{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:20:49Z","timestamp":1782789649976,"version":"3.54.5"},"reference-count":361,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The word opium derives from the ancient Greek word \u1f44\u03c0\u03b9\u03bf\u03bd (\u00f3pion) for the juice of any plant, but today means the air-dried seed capsule latex of Papaver somniferum. Alkaloid chemistry began with the isolation of morphine from crude opium by Friedrich Wilhelm Adam Sert\u00fcrner in 1804. More than a century later, Hungarian pharmacist J\u00e1nos Kabay opened new perspectives for the direct isolation of morphine from dry poppy heads and straw without the labor-intensive harvesting of opium. In 2015, Kabay\u2019s life and achievements obtained official recognition as constituting a \u00abHungarikum\u00bb, thereby entering the national repository of matters of unique cultural value. To this day, the study of Papaver alkaloids is a focus of medicinal chemistry, the (perhaps unstated) aspiration of which is to obtain an opioid with lesser abuse potential and side effects, while retaining good analgesic properties. We begin this review with a brief account of opiate biosynthesis, followed by a detailed presentation of semisynthetic opioids, emphasizing the efforts of the Alkaloida Chemical Company, founded in 1927 by J\u00e1nos Kabay, and the morphine alkaloid group of the University of Debrecen.<\/jats:p>","DOI":"10.3390\/ijms26062736","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T10:43:51Z","timestamp":1742294631000},"page":"2736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Morphinan Alkaloids and Their Transformations: A Historical Perspective of a Century of Opioid Research in Hungary"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9411-7899","authenticated-orcid":false,"given":"J\u00e1nos","family":"Marton","sequence":"first","affiliation":[{"name":"ABX Advanced Biochemical Compounds Biomedizinische Forschungsreagenzien GmbH, Heinrich-Glaeser-Strasse 10-14, D-01454 Radeberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-9621","authenticated-orcid":false,"given":"Paul","family":"Cumming","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Bern University Hospital, Freiburgstra\u00dfe 18, CH-3010 Bern, Switzerland"},{"name":"School of Psychology and Counselling, Queensland University of Technology, Brisbane, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenner C.","family":"Rice","sequence":"additional","affiliation":[{"name":"Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, NIDA and the NIAAA, NIH, Department of Health and Human Services, 9800 Medical Center Drive, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-6810","authenticated-orcid":false,"given":"Joannes T. M.","family":"Linders","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/andp.18170550104","article-title":"\u00dcber das Morphium, eine neue salzf\u00e4hige Grundlage, und die Mekons\u00e4ure, als Hauptbestandteile des Opiums","volume":"55","year":"1817","journal-title":"Ann. Der Phys."},{"key":"ref_2","first-page":"61","article-title":"Friedrich Wilhelm Sert\u00fcrner and the Discovery of Morphine","volume":"27","author":"Schmitz","year":"1985","journal-title":"Pharm. Hist."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2105\/AJPH.2007.131714","article-title":"The promotion and marketing of oxycontin: Commercial triumph, public health tragedy","volume":"99","year":"2009","journal-title":"Am. J. Publ. Health"},{"key":"ref_4","unstructured":"Kabay, J.J. (1990). J\u00e1nos Kabay, The Life of an Inventor."},{"key":"ref_5","unstructured":"Kabay, J.J. (1992). Kabay J\u00e1nos Magyar Feltal\u00e1l\u00f3 \u00c9lete, Alkaloida Vegy\u00e9szeti Gy\u00e1r R\u00e9szv\u00e9nyt\u00e1rsas\u00e1g."},{"key":"ref_6","first-page":"27","article-title":"Kabay J\u00e1nos a magyar morfingy\u00e1rt\u00e1s megalap\u00edt\u00f3ja","volume":"Volume 8","year":"1996","journal-title":"Kabay J\u00e1nosra Eml\u00e9kez\u00fcnk"},{"key":"ref_7","first-page":"25","article-title":"J\u00e1nos Kabay, the founder of morphine manufacture in Hungary","volume":"41","author":"Hosztafi","year":"1997","journal-title":"Gy\u00f3gyszer\u00e9szet"},{"key":"ref_8","unstructured":"Gazda, I. (2015). A Magyar K\u00e9mia \u00e9s Vegyipar Kronol\u00f3gi\u00e1ja 1800\u20131950, Magyar Tudom\u00e1nyt\u00f6rt\u00e9neti Int\u00e9zet Tudom\u00e1nyos K\u00f6zlem\u00e9nyei, Magyar Tudom\u00e1nyt\u00f6rt\u00e9neti Int\u00e9zet."},{"key":"ref_9","first-page":"169","article-title":"Kabay J\u00e1nos morfinel\u0151\u00e1ll\u00edt\u00e1si elj\u00e1r\u00e1sa","volume":"53","year":"1998","journal-title":"Magy. K\u00e9m. Lapja"},{"key":"ref_10","unstructured":"Kabay, J. (1925). Elj\u00e1r\u00e1s \u00d3piumalkaloid\u00e1k El\u0151\u00e1ll\u00edt\u00e1s\u00e1ra. (89,464), Hungarian Patent."},{"key":"ref_11","unstructured":"Kabay, J. (1931). Elj\u00e1r\u00e1s \u00d3piumalkaloid\u00e1k El\u0151\u00e1ll\u00edt\u00e1s\u00e1ra. (109,788), Hungarian Patent."},{"key":"ref_12","first-page":"21","article-title":"Manufacture of alkaloids from the poppy plant in Hungary","volume":"1","author":"Bayer","year":"1961","journal-title":"Bull. Narc."},{"key":"ref_13","first-page":"423","article-title":"A magyar alkaloidk\u00e9mia t\u00f6rt\u00e9nete","volume":"100","author":"Nemes","year":"1994","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_14","unstructured":"Bern\u00e1th, J. (1998). Poppy, The Genus Papaver, Harwood Academic Publishers."},{"key":"ref_15","first-page":"235","article-title":"Bogn\u00e1r Rezs\u0151 szerves k\u00e9mikus egyetemi tan\u00e1r, akad\u00e9mikus, tudom\u00e1nypolitikus (1913\u20131990)","volume":"7","author":"Herczegh","year":"2016","journal-title":"Gerund. Egyetemt\u00f6rt\u00e9neti K\u00f6zlem\u00e9nyek"},{"key":"ref_16","unstructured":"Bogn\u00e1r, R., Ga\u00e1l, G.D., M\u00e9sz\u00e1ros, Z., Szab\u00f3, S., and Zeller, I. (1958). Elj\u00e1r\u00e1s Morphin T\u00e1rsalkaloidjainak Kinyer\u00e9s\u00e9re M\u00e1kn\u00f6v\u00e9ny R\u00e9szeinek Kivonatol\u00e1sa Sor\u00e1n Kapott Anyagb\u00f3l. (145,999), Hungarian Patent."},{"key":"ref_17","unstructured":"Szl\u00e1vik, L., Bogn\u00e1r, R., Bart\u00f3k, A., Ga\u00e1l, G., Kask\u00f6t\u0151, Z., Nagy, S., Gy\u00f6ngy, I., Maczk\u00f3, G., Kerekes, P., and Selmeci, G. (1967). Elj\u00e1r\u00e1s \u00d3piumalkaloid\u00e1k El\u0151\u00e1ll\u00edt\u00e1s\u00e1ra. (155,407), Hungarian Patent."},{"key":"ref_18","first-page":"452","article-title":"On the accompanying alkaloids of morphine 1. Isolation of codeine, thebaine and narcotine","volume":"22","author":"Kerekes","year":"1967","journal-title":"Pharmazie"},{"key":"ref_19","first-page":"525","article-title":"On the companion alkaloids of morphine. 2. Isolation of narcotoline and papaverine","volume":"22","year":"1967","journal-title":"Pharmazie"},{"key":"ref_20","first-page":"590","article-title":"On the accompanying alkaloids of morphine. 3. Modified preparation of codeine, thebaine and papaverine","volume":"23","year":"1968","journal-title":"Pharmazie"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1021\/np50020a001","article-title":"The phthtalideisoquinoline alkaloids","volume":"45","author":"Gula","year":"1982","journal-title":"J. Nat. Prod."},{"key":"ref_22","unstructured":"Bentley, K.W. (1954). The Chemistry of Morphine Alkaloids, Clarendon Press."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Casy, A.F., and Parfitt, R.T. (1986). Diels-Alder adducts of thebaine. Opioid Analgesics: Chemistry and Receptors, Plenum Press.","DOI":"10.1007\/978-1-4899-0585-7"},{"key":"ref_24","first-page":"128","article-title":"The morphine alkaloids","volume":"Volume 45","year":"1994","journal-title":"The Alkaloids: Chemistry and Physiology"},{"key":"ref_25","unstructured":"Bern\u00e1th, J. (1998). III. Chemistry-Biochemistry of Poppy, 1. Chemical Structures of Alkaloids. Poppy, The Genus Papaver, Harwood Academic Publishers."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s13258-023-01477-4","article-title":"O- and N-Methyltransferases in benzylisoquinoline alkaloid producing plants","volume":"46","author":"Lee","year":"2023","journal-title":"Genes Genom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1104\/pp.88.1.52","article-title":"Elicitor-Induced l-Tyrosine Decarboxylase from Plant Cell Suspension Cultures: II. Partial Characterization","volume":"88","author":"Marques","year":"1988","journal-title":"Plant Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1104\/pp.111.185512","article-title":"Tyrosine aminotransferase contributes to benzylisoquinoline alkaloid biosynthesis in opium poppy","volume":"157","author":"Lee","year":"2011","journal-title":"Plant Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10153","DOI":"10.1021\/bi700752n","article-title":"Mechanistic studies on norcoclaurine synthase of benzylisoquinoline alkaloid biosynthesis: An enzymatic Pictet-Spengler reaction","volume":"46","author":"Luk","year":"2007","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/tpj.13225","article-title":"Crystal structure of norcoclaurine-6-O-methyltransferase, a key rate-limiting step in the synthesis of benzylisoquinoline alkaloids","volume":"87","author":"Robin","year":"2016","journal-title":"Plant J."},{"key":"ref_31","first-page":"1457","article-title":"cDNA cloning and characterization of (S)-N-methylcoclaurine 3\u2032-hydroxylase (CYP80B1) from elicitortreated opium poppy cell suspension cultures (accession no. AF191772)","volume":"122","author":"Yu","year":"2000","journal-title":"Plant Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/mds.1246","article-title":"Toxicity of Annonaceae for dopaminergic neurons: Potential role in atypical parkinsonism in Guadeloupe","volume":"17","author":"Lannuzel","year":"2002","journal-title":"Mov. Disord."},{"key":"ref_33","unstructured":"Bern\u00e1th, J. (1998). Pharmacology of poppy alkaloids. Poppy\u2014The Genus Papaver, Harwood Academic Publisher."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0014-2999(98)00862-0","article-title":"Stereoselective mu- and delta-opioid receptor-related antinociception and binding with (+)-thebaine","volume":"365","author":"Aceto","year":"1999","journal-title":"Eur. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Cumming, P., Marton, J., Lilius, T.O., Olberg, D.E., and Rominger, A. (2019). A Survey of Molecular Imaging of Opioid Receptors. Molecules, 24.","DOI":"10.3390\/molecules24224190"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1055\/s-0028-1097192","article-title":"Papaver bracteatum\u2014A summary of current knowledge","volume":"35","author":"Nyman","year":"1979","journal-title":"Planta Med."},{"key":"ref_37","unstructured":"Bern\u00e1th, J. (1998). An alternative raw-the cultivation and breeding of Papaver bracteatum. Poppy\u2014The Genus Papaver, Harwood Academic Press."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/431413a","article-title":"Morphine-pathway block in top1 poppies","volume":"431","author":"Millgate","year":"2004","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1111\/tpj.13975","article-title":"Codeinone reductase isoforms with differential stability, efficiency and product selectivity in opium poppy","volume":"95","author":"Dastmalchi","year":"2018","journal-title":"Plant J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1105\/tpc.015396","article-title":"A tale of three cell types: Alkaloid biosynthesis is localized to sieve elements in opium poppy","volume":"15","author":"Bird","year":"2003","journal-title":"Plant Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1105\/tpc.113.115113","article-title":"Morphine biosynthesis in opium poppy involves two cell types: Sieve elements and laticifers","volume":"25","author":"Onoyovwe","year":"2013","journal-title":"Plant Cell"},{"key":"ref_42","unstructured":"Lim, H.-Y., and Kwok, S.-F. (1981). Differentiation and Comparison of Raw, Prepared and Dross Opium, United Nations Office on Drugs and Crime. Available online: https:\/\/www.unodc.org\/unodc\/en\/data-and-analysis\/bulletin\/bulletin_1981-01-01_1_page006.html."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.indcrop.2012.04.018","article-title":"Analysis of selected poppy (Papaver somniferum L.) cultivars: Pharmaceutically important alkaloids","volume":"41","author":"Stranska","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Carlin, M.G., Dean, J.R., and Ames, J.M. (2020). Opium alkaloids in harvested and thermally processed poppy seeds. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.00737"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s40122-019-0113-5","article-title":"Poppy Seed Tea: A Short Review and Case Study","volume":"8","author":"Haber","year":"2019","journal-title":"Pain Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1093\/jat\/bkaa093","article-title":"Death from poppy tea consumption","volume":"44","author":"Fox","year":"2020","journal-title":"J. Anal. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/BF00201114","article-title":"Fatal intoxications in Denmark following intake of morphine from opium poppies","volume":"101","author":"Steentoft","year":"1988","journal-title":"Z. Rechtsmed."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1080\/15563650.2023.2271163","article-title":"Toxicokinetics of thebaine in those consuming non-food grade poppy seeds as a tea","volume":"61","author":"Penafiel","year":"2023","journal-title":"Clin. Toxicol."},{"key":"ref_49","first-page":"17","article-title":"Biochemistry of opioid (morphine) receptors: Binding, structure and molecular modelling","volume":"59","author":"Benyhe","year":"2015","journal-title":"Acta Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1056402","DOI":"10.3389\/fphar.2023.1056402","article-title":"The role of opioid receptors in modulating Alzheimer\u2019s Disease","volume":"14","author":"Tanguturi","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1126\/scisignal.aav0320","article-title":"Biased ligands at opioid receptors: Current status and future directions","volume":"14","author":"Che","year":"2021","journal-title":"Sci. Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1039\/D1MD00041A","article-title":"Comprehensive overview of biased pharmacology at the opioid receptors: Biased ligands and bias factors","volume":"12","author":"Barlow","year":"2021","journal-title":"RSC Med. Chem."},{"key":"ref_53","first-page":"115","article-title":"Metabolism and disposition of prescription opioids: A review","volume":"27","author":"DePriest","year":"2015","journal-title":"Forensic Sci. Rev."},{"key":"ref_54","first-page":"289","article-title":"Amino-morfidok \u00e9s amino-kodidok el\u0151\u00e1ll\u00edt\u00e1s\u00e1nak \u00e9s t\u00e9rk\u00e9mi\u00e1j\u00e1nak vizsg\u00e1lat\u00e1r\u00f3l","volume":"30","author":"Makleit","year":"1968","journal-title":"K\u00e9m. K\u00f6zl."},{"key":"ref_55","first-page":"203","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group II. Aminomorphides and aminocodides","volume":"58","author":"Makleit","year":"1968","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/recl.19841031005","article-title":"Synthesis of 6, 14-ethenoisomorphinans and 6, 14-ethenomorphinans based on Diels\u2013Alder adducts of 6-demethoxythebaine and 6-demethoxy-\u03b2-dihydrothebaine; pharmacology of the isomorphinans (Chemistry of Opium Alkaloids, Part XIX)","volume":"103","author":"Crabbendam","year":"1984","journal-title":"Recl. Trav. Chim. Pays-Bas"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Marton, J., Fekete, A., Cumming, P., Hosztafi, S., Mikecz, P., and Henriksen, G. (2022). Diels\u2013Alder adducts of morphinan-6, 8-dienes and their transformations. Molecules, 27.","DOI":"10.3390\/molecules27092863"},{"key":"ref_58","first-page":"305","article-title":"L\u2019importance des ethers alcoyliques des acides sulfoaromatiquea pour l\u2019alcoylation des composes organiques","volume":"39","author":"Rodionov","year":"1926","journal-title":"Bull. Soc. Chim. Fr."},{"key":"ref_59","first-page":"15","article-title":"The manufacture of codeine from morphine","volume":"10","author":"Heumann","year":"1958","journal-title":"Bull. Narcotics"},{"key":"ref_60","unstructured":"Gy\u00f6ngy, I., Makleit, S., M\u00e9sz\u00e1ros, Z., and Szl\u00e1vik, L. (1956). Elj\u00e1r\u00e1s Folcodin (Morfolinil-Etil-Morfin) El\u0151\u00e1ll\u00edt\u00e1s\u00e1ra. (144,637), Hungarian Patent."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bja.2023.02.026","article-title":"Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: The ALPHO case-control study","volume":"131","author":"Mertes","year":"2023","journal-title":"Br. J. Anaesth."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1136\/bmj.p609","article-title":"UK withdraws pholcodine-containing cough and cold medicines over anaphylaxis risk in surgery","volume":"380","author":"Mahase","year":"2023","journal-title":"BMJ Brit. Med. J."},{"key":"ref_63","unstructured":"Szab\u00f3, S., and Bogn\u00e1r, R. (1956). Elj\u00e1r\u00e1s N-allil-normorfin tiszt\u00edt\u00e1s\u00e1ra. (1483), Hungarian Patent."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1021\/ja01846a504","article-title":"The Preparation of N-Allylnormorphine","volume":"63","author":"McCawley","year":"1941","journal-title":"J. Am. Chem. Soc."},{"key":"ref_65","first-page":"1438","article-title":"Die Einwirkung von Bromcyan auf terti\u00e4re Amine","volume":"33","year":"1900","journal-title":"Berichte"},{"key":"ref_66","first-page":"363","article-title":"A New route for the preparation of N-substituted N-demethylapocodeine derivatives","volume":"110","author":"Hosztafi","year":"1982","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_67","first-page":"51","article-title":"Preparation of demethoxyoripavine and its conversion into N-substituted N-demethylapomorphine derivatives","volume":"113","author":"Hosztafi","year":"1983","journal-title":"Acta Chim. Hung."},{"key":"ref_68","unstructured":"Bogn\u00e1r, R., and Makleit, S. (1956). A new preparation of dihydro-6-deoxymorphine. Chem. Ind., 1239."},{"key":"ref_69","first-page":"323","article-title":"Eine neue Darstellung des Dihydro-6-desoxymorphins","volume":"8","author":"Makleit","year":"1958","journal-title":"Arzneim. Forsch.\/Drug. Res."},{"key":"ref_70","first-page":"225","article-title":"A dihidro-6-desoxymorphin \u00faj el\u0151\u00e1ll\u00edt\u00e1sa","volume":"5","author":"Makleit","year":"1958","journal-title":"Acta Univ. Debreceniensis Ludovico Kossuth Nomin."},{"key":"ref_71","first-page":"2","article-title":"The Morphine Alkaloids I","volume":"Volume 2","author":"Manske","year":"1952","journal-title":"The Alkaloids, Chemistry and Physiology"},{"key":"ref_72","first-page":"162","article-title":"The Morphine Alkaloids II","volume":"Volume 2","author":"Manske","year":"1952","journal-title":"The Alkaloids, Chemistry and Physiology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1021\/jo01223a011","article-title":"Reduction studies in the morphine series. VII. Thebaine","volume":"3","author":"Small","year":"1939","journal-title":"J. Org. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1021\/ja01123a055","article-title":"The reduction of thebaine","volume":"74","author":"Stork","year":"1952","journal-title":"J. Am. Chem. Soc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/BF02152875","article-title":"Some notes on the reduction of thebaine and related topics","volume":"65","author":"Bentley","year":"1950","journal-title":"Experientia"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bentley, K.W., Robinson, R., and Wain, A.E. (1952). The reduction of thebaine and dihydrothebaine by sodium and ammonia. J. Chem. Soc., 958\u2013966.","DOI":"10.1039\/jr9520000958"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3604","DOI":"10.1021\/jo00412a043","article-title":"Synthesis of \u03b2-dihydrothebaine","volume":"43","author":"Razdan","year":"1978","journal-title":"J. Org. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/hlca.19500330413","article-title":"\u00dcber das \u03b2-Dihydro-thebain","volume":"33","author":"Schmid","year":"1950","journal-title":"Helv. Chim. Acta"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1039\/j39690001945","article-title":"Reduction of thebaine with mixed hydride reducing agents","volume":"15","author":"Bentley","year":"1969","journal-title":"J. Chem. Soc. C"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/recl.19861050104","article-title":"Scission of the epoxy ring in 4.5\u03b1-epoxymorphinans: A convenient synthesis of \u03b2-dihydrothebaine, 6-demethoxy-\u03b2-dihydrothebaine and desoxycodeine-A. (Chemistry of Opium Alkaloids, Part 21)","volume":"105","author":"Linders","year":"1986","journal-title":"Recl. Trav. Chim. Pays-Bas"},{"key":"ref_81","first-page":"5","article-title":"Address of the President Sir Robert Robinson, at the anniversary meeting, 1 December 1947","volume":"135","author":"Robinson","year":"1947","journal-title":"Proc. Roy. Soc. Lond. Ser. B Biol. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/160815a0","article-title":"An essay in correlation arising from alkaloid chemistry","volume":"160","author":"Robinson","year":"1947","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1021\/jo01125a020","article-title":"The reduction of thebaine. Neopine methyl ether","volume":"20","author":"Small","year":"1955","journal-title":"J. Org. Chem."},{"key":"ref_84","first-page":"321","article-title":"A tebain hidrog\u00e9nez\u00e9s\u00e9r\u0151l","volume":"59","year":"1953","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_85","unstructured":"Szab\u00f3, S. (1967). \u00dajabb Adatok a Tebain Redukci\u00f3s Term\u00e9keinek K\u00e9mi\u00e1j\u00e1hoz. [C.Sc. Dissertation, Kossuth Lajos Tudom\u00e1nyegyetem (KLTE)]."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/jlac.19274520114","article-title":"Die Konstitution der Morphiumalkaloide","volume":"452","year":"1927","journal-title":"Justus Liebigs Ann. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.drugalcdep.2016.12.021","article-title":"Desomorphine (Krokodil): An overview of its chemistry, pharmacology, metabolism, toxicology and analysis","volume":"173","author":"Florez","year":"2017","journal-title":"Drug Alcohol Depend."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1021\/acschemneuro.0c00495","article-title":"DARK classics in chemical neuroscience: Krokodil","volume":"11","author":"Alves","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3905","DOI":"10.1021\/acschemneuro.0c00262","article-title":"DARK classics in chemical neuroscience: Heroin and desomorphine","volume":"11","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.1021\/ja01155a552","article-title":"\u03947-Desoxymorphine","volume":"73","author":"Rapoport","year":"1951","journal-title":"J. Am. Chem. Soc."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1021\/jm701457j","article-title":"Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3-and 6-substituted morphine analogs","volume":"51","author":"Cunningham","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_92","first-page":"353","article-title":"Synthetic substances with morphine-like effect: Relationship between analgesic action and addiction liability, with a discussion of the chemical structure of addiction-producing substances","volume":"14","author":"Eddy","year":"1956","journal-title":"Bull. World Health Org."},{"key":"ref_93","first-page":"937","article-title":"Synthetic substances with morphine-like effect: Relationship between chemical structure and analgesic action","volume":"13","author":"Braenden","year":"1955","journal-title":"Bull. World Health Org."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1021\/jm00189a007","article-title":"Deoxymorphines: Role of the phenolic hydroxyl in antinociception and opiate receptor interactions","volume":"22","author":"Reden","year":"1979","journal-title":"J. Med. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.forsciint.2015.02.001","article-title":"The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity","volume":"249","author":"Alves","year":"2015","journal-title":"Forensic Sci. Int."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.lfs.2014.03.008","article-title":"A \u201cKrokodil\u201d emerges from the murky waters of addiction. Abuse trends of an old drug","volume":"102","author":"Katselou","year":"2014","journal-title":"Life Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1021\/ja01334a042","article-title":"The desoxymorphines","volume":"55","author":"Small","year":"1933","journal-title":"J. Am. Chem. Soc."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1021\/ja01336a073","article-title":"The catalytic hydrogenation of the halogenomorphides: Dihydrodesoxymorphine-D","volume":"55","author":"Small","year":"1933","journal-title":"J. Am. Chem. Soc."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1021\/jo01374a001","article-title":"O3-Monoacetylacetylmorphine","volume":"19","author":"Welsh","year":"1954","journal-title":"J. Org. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1002\/hlca.19490320504","article-title":"\u00dcber die Umsetzungsprodukte von Toluolsulfons\u00e4ureestern mit Lithiumaluminiumhydrid","volume":"32","author":"Schmid","year":"1949","journal-title":"Helv. Chim. Acta"},{"key":"ref_101","first-page":"409","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, XIV. A new method for the preparation of \u201cdeoxymorphine E and dihydrodeoxymorphine D\u201d","volume":"88","author":"Makleit","year":"1976","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00706-011-0635-y","article-title":"A facile and improved synthesis of desomorphine and its deuterium-labeled analogue","volume":"143","author":"Srimurugan","year":"2012","journal-title":"Monatsh. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/10550887.2012.735570","article-title":"Desomorphine goes \u201ccrocodile\u201d","volume":"31","author":"Gahr","year":"2012","journal-title":"J. Addict. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.dib.2015.11.046","article-title":"Data analysis of \u201ckrokodil\u201d samples obtained by street-like synthesis","volume":"6","author":"Neves","year":"2015","journal-title":"Data Brief"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5348\/100901Z01SB2018CR","article-title":"New case of krokodil (desomorphine) use","volume":"9","author":"Caldararo","year":"2018","journal-title":"Int. J. Case Rep. Images"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1021\/acs.chemrestox.7b00126","article-title":"Street-like synthesis of krokodil results in the formation of an enlarged cluster of known and new morphinans","volume":"30","author":"Soares","year":"2017","journal-title":"Chem. Res. Toxicol."},{"key":"ref_107","unstructured":"Smith, M.B. (2013). Reactions, Mechanisms, and Structure, Chapter 10. Aliphatic substitution nucleophilic and organometallic. March\u2019s Advanced Organic Chemistry, John Wiley & Sons Inc.. [7th ed.]."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1002\/cphc.201701363","article-title":"Nucleophilic substitution (SN2): Dependence on nucleophile, leaving group, central atom, substituents, and solvent","volume":"19","author":"Hamlin","year":"2018","journal-title":"ChemPhysChem"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/bc500475e","article-title":"Fluorine-18 radiochemistry, labeling strategies and synthetic routes","volume":"26","author":"Jacobson","year":"2015","journal-title":"Bioconjugate Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4619","DOI":"10.1021\/ja01599a026","article-title":"The SN2\u2032 reaction. III. Structure and SN2\u2032 reactions of the halocodides","volume":"78","author":"Stork","year":"1956","journal-title":"J. Am. Chem. Soc."},{"key":"ref_111","first-page":"461","article-title":"Tozil-, ill. mezilsz\u00e1rmaz\u00e9kok reakci\u00f3inak vizsg\u00e1lata a morfinsorban, VIII. A 6-dezoxi-6-fluor-izo-kodein \u00faj el\u0151\u00e1ll\u00edt\u00e1sa \u00e9s vizsg\u00e1lata","volume":"76","author":"Makleit","year":"1970","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_112","first-page":"63","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, VIII. A new synthesis and investigations of 6-deoxy-6-fluoroisocodeine","volume":"67","author":"Makleit","year":"1971","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_113","first-page":"564","article-title":"Tozil-, ill. mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XVI. \u00dajabb adatok az allil\u00e1trendez\u0151d\u00e9s mechanizmus\u00e1hoz","volume":"81","author":"Makleit","year":"1975","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_114","first-page":"275","article-title":"Conversions of tosyl and mesyl derivatives in the morphine group, XVI. New data to the mechanism of allylic rearrangement","volume":"89","author":"Makleit","year":"1976","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_115","unstructured":"Makleit, S. (1972). Az un Morfin-Sor (Morfin, Kodein, Dihidromorfin, Dihidrokodein, 14-Hidroxi-Kodein \u00e9s 14-Hidroxi-Dihidrokodein) 6-O-Tozil, ill, 6-O-Mezil-Sz\u00e1rmaz\u00e9kai El\u0151\u00e1ll\u00edt\u00e1sa \u00e9s Nukleofil Szubsztit\u00faci\u00f3s Reakci\u00f3inak Tanulm\u00e1nyoz\u00e1sa, Part I (1971), Part 2 (1972). [D.Sc. Dissertation, Kossuth Lajos University]."},{"key":"ref_116","unstructured":"Ga\u00e1l, G. (1973). 2.1. M\u00e1kalkaloidok izol\u00e1l\u00e1sa \u00e9s k\u00e9miai \u00e1talak\u00edt\u00e1sa. Kutat\u00e1si eredm\u00e9nyek 1950\u20131973, Jubileumi K\u00f6tet Bogn\u00e1r Rezs\u0151 Hatvanadik Sz\u00fclet\u00e9snapj\u00e1ra, Kossuth Lajos Tudom\u00e1nyegyetem Szerves K\u00e9miai Tansz\u00e9ke; Alf\u00f6ldi Nyomda."},{"key":"ref_117","first-page":"523","article-title":"Tozil-, ill. mezilsz\u00e1rmaz\u00e9kok reakci\u00f3inak vizsg\u00e1lata a morfinsorban, III. Azido- \u00e9s amino-kodidok el\u0151\u00e1ll\u00edt\u00e1sa","volume":"74","author":"Makleit","year":"1968","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_118","first-page":"373","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, III. Preparation of azido- and aminocodides","volume":"59","author":"Makleit","year":"1969","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_119","first-page":"526","article-title":"Tozil-, ill. mezilsz\u00e1rmaz\u00e9kok reakci\u00f3nak vizsg\u00e1lata a morfinsorban, IV. Azido-\u00e9s amino-morfidok el\u0151\u00e1ll\u00edt\u00e1sa","volume":"74","author":"Makleit","year":"1968","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_120","first-page":"379","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, IV. Preparation of \u201cazido- and aminomorphides\u201d","volume":"59","author":"Makleit","year":"1969","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_121","first-page":"223","article-title":"Tozil-, illetve mezilsz\u00e1rmaz\u00e9kok reakci\u00f3inak vizsg\u00e1lata a morfinsorban, X. 14-Hidroxi-morfin-sz\u00e1rmaz\u00e9kok, I. Azido- \u00e9s aminovegy\u00fcletek","volume":"78","author":"Makleit","year":"1972","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_122","first-page":"99","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, X. 14-Hydroxymorpine derivatives, I. Azido and amino derivatives","volume":"74","author":"Makleit","year":"1972","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_123","first-page":"235","article-title":"Tozil-, ill. mezilsz\u00e1rmaz\u00e9kok reakci\u00f3inak vizsg\u00e1lata a morfinsorban, V. Izo-kodein \u00e9s dihidro-izo-kodein \u00faj el\u0151\u00e1ll\u00edt\u00e1sa","volume":"75","author":"Makleit","year":"1969","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_124","first-page":"387","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, V. A new method for the preparation of isocodeine and dihydroisocodeine","volume":"59","author":"Makleit","year":"1969","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_125","first-page":"330","article-title":"Tozil-, ill. mezil-sz\u00e1rmaz\u00e9kok reakci\u00f3inak vizsg\u00e1lata a morfin-sorban. Acetil-merkapto \u00e9s merkaptosz\u00e1rmaz\u00e9kok el\u0151\u00e1ll\u00edt\u00e1sa","volume":"75","author":"Makleit","year":"1969","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_126","first-page":"161","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group. Synthesis of acetylmercapto and mercapto derivatives","volume":"59","author":"Makleit","year":"1969","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_127","first-page":"102","article-title":"Tozil ill. mezilsz\u00e1rmaz\u00e9kok reakci\u00f3inak vizsg\u00e1lata a morfinsorban, VI. Acetilmerkapto \u00e9s merkaptosz\u00e1rmaz\u00e9kok el\u0151\u00e1ll\u00edt\u00e1sa","volume":"76","author":"Makleit","year":"1970","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_128","first-page":"273","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, VI. Synthesis of acetylmercapto and mercapto derivatives","volume":"64","author":"Makleit","year":"1970","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_129","first-page":"517","article-title":"Tozil, illetve mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XV.: A pszeudokodein-tozil\u00e1t nukleofil szubsztit\u00faci\u00f3s reakci\u00f3inak tanulm\u00e1nyoz\u00e1sa","volume":"81","author":"Makleit","year":"1975","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_130","first-page":"173","article-title":"Conversions of tosyl and mesyl derivatives in the morphine group XV. Nucleophilic substitution reactions of pseudocodeine tosylate","volume":"82","author":"Makleit","year":"1976","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_131","first-page":"112","article-title":"Tozil-, illetve mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, VII. Izo-morfin \u00e9s dihidro-izo-morfin \u00faj el\u0151\u00e1ll\u00edt\u00e1sa","volume":"76","author":"Makleit","year":"1970","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_132","first-page":"281","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, VII. A new method for the preparation of isomorphine and dihydroisomorphine","volume":"64","author":"Makleit","year":"1970","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_133","first-page":"163","article-title":"Tozil-, ill. mezilsz\u00e1rmaz\u00e9kok reakci\u00f3inak vizsg\u00e1lata a morfinsorban, IX","volume":"78","author":"Makleit","year":"1972","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/BF00912938","article-title":"Reaktionen von Tosyl- bzw. Mesyl-Derivaten in der Morphin-Reihe, 9. Mitt","volume":"103","author":"Makleit","year":"1972","journal-title":"Monatsh. Chem."},{"key":"ref_135","unstructured":"Small, L.F., and Lutz, R.E. (1932). Chemistry of the Opium Alkaloids."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1248\/cpb.18.1569","article-title":"Synthesis of B\/C trans-fused morphine structures. IV. Synthesis of B\/C trans-isomorphine","volume":"18","author":"Inoue","year":"1970","journal-title":"Chem. Pharm. Bull."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1021\/jm00299a043","article-title":"Synthesis of B\/C trans-fused morphine structures. V. Pharmacological summary of trans-morphine derivatives and an improved synthesis of trans-codeine","volume":"13","author":"Kugita","year":"1970","journal-title":"J. Med. Chem."},{"key":"ref_138","first-page":"478","article-title":"\u00daj, hat\u00e9kony m\u00f3dszer neopin el\u0151\u00e1ll\u00edt\u00e1s\u00e1ra","volume":"83","author":"Makleit","year":"1977","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_139","first-page":"165","article-title":"A new and efficient method for the preparation of neopine","volume":"94","author":"Makleit","year":"1977","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_140","first-page":"335","article-title":"Az izoneopin el\u0151\u00e1ll\u00edt\u00e1sa","volume":"86","author":"Makleit","year":"1980","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_141","first-page":"97","article-title":"Synthesis of isoneopine","volume":"104","author":"Makleit","year":"1980","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_142","first-page":"87","article-title":"Morphine alkaloids Part 105. Isolation of neopine from poppy head","volume":"25","author":"Makleit","year":"1986","journal-title":"Herba Hung."},{"key":"ref_143","first-page":"499","article-title":"Tozil-, illetve mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XXII. A 6-O-mezil-neopin n\u00e9h\u00e1ny nukleofil szubsztit\u00faci\u00f3s reakci\u00f3ja","volume":"85","author":"Makleit","year":"1979","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_144","first-page":"365","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, XXII. Some nucleophilic substitution reactions of 6-O-mesylneopine","volume":"103","author":"Makleit","year":"1980","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/recl.19811000711","article-title":"Chemistry of opium alkaloids. Part XV. Preparation of 6-demethoxythebaine from neopine and its Diels-Alder reaction with ethyl acrylate","volume":"100","author":"Crabbendam","year":"1981","journal-title":"Recl. Trav. Chim. Pays-Bas"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1021\/jm00139a002","article-title":"6-Demethoxythebaine and its conversion to analgesics of the 6,14-ethenomorphinan type","volume":"24","author":"Hutchins","year":"1981","journal-title":"J. Med. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/recl.19841030403","article-title":"Convenient conversions of codeine into 6-demethoxythebaine via bond rearrangement (Chemistry of Opium Alkaloids, Part XVIII)","volume":"103","author":"Beyerman","year":"1984","journal-title":"Recl. Trav. Chim. Pays-Bas"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1021\/jm00256a019","article-title":"14-Hydroxycodeinone. Improved synthesis","volume":"17","author":"Hauser","year":"1974","journal-title":"J. Med. Chem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1021\/jm00202a018","article-title":"Studies in the (+)-morphinan series. 5. Synthesis and biological properties of (+)-naloxone","volume":"21","author":"Iijima","year":"1978","journal-title":"J. Med. Chem."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Currie, A.C., Gillon, J., Newbold, G.T., and Spring, F.S. (1960). Some reactions of 14-hydroxycodeine. J. Chem. Soc., 773\u2013781.","DOI":"10.1039\/jr9600000773"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1248\/cpb.14.445","article-title":"Studies on the morphine alkaloids and its related compounds. XIII. On the nucleophilic substitution reactions of the 14-hydroxylated morphine alkaloids","volume":"14","author":"Seki","year":"1966","journal-title":"Chem. Pharm. Bull."},{"key":"ref_152","first-page":"402","article-title":"Tozil \u00e9s mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XXV. A 6-O-mezil-7\u03b1-kl\u00f3r(br\u00f3m)-neopin nukleofil szubsztit\u00faci\u00f3s reakci\u00f3inak vizsg\u00e1lata","volume":"92","author":"Simon","year":"1986","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_153","first-page":"497","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, XXV. Studies of the nucleophilic substitution reactions of 6-O-mesyl-7\u03b1-chloro(bromo)neopine","volume":"124","author":"Simon","year":"1987","journal-title":"Acta Chim. Hung."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1016\/S0040-4020(01)98160-8","article-title":"Studies on morphine alkaloids\u2014VIII. Some reactions of 14\u03b2-bromocodeine and related compounds","volume":"27","author":"Abe","year":"1971","journal-title":"Tetrahedron"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"5960","DOI":"10.1021\/ja01627a052","article-title":"Neopinone","volume":"77","author":"Conroy","year":"1955","journal-title":"J. Am. Chem. Soc."},{"key":"ref_156","unstructured":"Ber\u00e9nyi, S. (1984). A 8,14-es Helyzetben Kett\u0151s K\u00f6t\u00e9st \u00e9s Kett\u0151sen Allil-Rendszert Tartalmaz\u00f3 Morfinsz\u00e1rmaz\u00e9kok SN T\u00edpus\u00fa Reakci\u00f3i;. [C.Sc. Dissertation, Kossuth Lajos Tudom\u00e1nyegyetem Debrecen]."},{"key":"ref_157","first-page":"154","article-title":"Tozil- \u00e9s mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XXIII. \u00daj 6-szubsztitu\u00e1lt-6-demetoxi-tebain sz\u00e1rmaz\u00e9kok el\u0151\u00e1ll\u00edt\u00e1sa","volume":"90","author":"Makleit","year":"1984","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_158","first-page":"307","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, XXIII. Preparation of new 6-substtituted-6-demethoxythebaine derivatives","volume":"117","author":"Makleit","year":"1984","journal-title":"Acta Chim. Hung."},{"key":"ref_159","first-page":"275","article-title":"Morphine Alkaloids. Part 106. Reactions of morphine derivatives containing double allylic system. Part 2. Studies of nucleophilic substitution reactions of dihalo derivatives","volume":"126","author":"Makleit","year":"1989","journal-title":"Acta. Chim. Hung."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1248\/cpb.13.1092","article-title":"Studies on morphine alkaloids. II. Indolinocodeine. I. A new skeletal rearrangement of 14-bromocodeine","volume":"13","author":"Okuda","year":"1965","journal-title":"Chem. Pharm. Bull."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Patai, S. (1971). The chemistry of the azido group. The Chemistry of Functional Groups, Interscience Publishers a division of John Wiley & Sons Ltd.","DOI":"10.1002\/9780470771266"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"5188","DOI":"10.1002\/anie.200400657","article-title":"Organic azides: An exploding diversity of a unique class of compounds","volume":"44","author":"Braese","year":"2005","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Braese, S., and Banert, K. (2010). Part 1. Synthesis and safety, Chapter 3. Synthesis of azides. Organic Azides. Syntheses and Applications, John Wiley & Sons, Ltd.","DOI":"10.1002\/9780470682517"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1021\/acs.accounts.0c00046","article-title":"Electrophilic azides for materials synthesis and chemical biology","volume":"53","author":"Xie","year":"2020","journal-title":"Acc. Chem. Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"6062","DOI":"10.1039\/D1CC01143J","article-title":"Nucleophilic transformations of azido-containing carbonyl compounds via protection of the azido group","volume":"57","author":"Aimi","year":"2021","journal-title":"Chem. Commun."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0079-6468(08)70020-1","article-title":"Chapter 3. The medicinal chemistry of the azido group","volume":"Volume 31","author":"Ellis","year":"1994","journal-title":"Progress in Medicinal Chemistry"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Cocker, J.D., Cowley, B.R., Cox, J.S.G., Eardley, S., Gregory, G.I., Lazenby, J.K., Long, A.G., Sly, J.C.P., and Somerfield, G.A. (1965). 922. Cephalosporanic acids. Part II. Displacement of the acetoxy-group by nucleophiles. J. Chem. Soc., 5015\u20135031.","DOI":"10.1039\/jr9650005015"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"64","DOI":"10.7164\/antibiotics.25.64","article-title":"7-(\u03b1-aminophenylacetamido)-3-azidomethyl-3-cephem-4-carboxylic acid","volume":"25","author":"Willner","year":"1972","journal-title":"J. Antibiot."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0166-2236(87)90160-3","article-title":"Is Ro 15-4513 a specific alcohol antagonist?","volume":"10","author":"Lister","year":"1987","journal-title":"Trends Neurosci."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Bach, P., de Timary, P., Gr\u00fcnder, G., and Cumming, P. (2023). Molecular imaging studies of alcohol use disorder. Current Topics in Behavioral Neurosciences, Springer.","DOI":"10.1007\/7854_2022_414"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/BF02245279","article-title":"[11C]Ro 15-4513, a ligand for visualization of benzodiazepine receptor binding. Preparation, autoradiography and positron emission tomography","volume":"108","author":"Halldin","year":"1992","journal-title":"Psychopharmacology"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S0026-895X(25)12766-1","article-title":"A photochemical affinity-labelling reagent for the opiate receptor (s)","volume":"8","author":"Winter","year":"1972","journal-title":"Mol. Pharmacol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2174\/092986730106220216112120","article-title":"Structure-activity relationships of synthetic and semisynthetic opioid agonists and antagonists","volume":"1","author":"Hosztafi","year":"1995","journal-title":"Curr. Med. Chem."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1556\/APhysiol.95.2008.1.1","article-title":"The chemical and pharmacological importance of morphine analogues","volume":"95","author":"Hosztafi","year":"2008","journal-title":"Acta Physiol. Hung."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0031-6989(73)80035-9","article-title":"Azidomorphine and rymazolium an approach to the ideal analgesic","volume":"5","author":"Knoll","year":"1973","journal-title":"Pharmacol. Res. Commun."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0364-7722(79)90074-2","article-title":"Azidomorphines: A new family of potent analgesics with low dependence capacity","volume":"3","author":"Knoll","year":"1979","journal-title":"Prog. Neuropsychopharmacol."},{"key":"ref_177","unstructured":"Knoll, J., F\u00fcrst, S., M\u00e9sz\u00e1ros, Z., Nagy, G., D\u00e1vid, \u00c1., Bogn\u00e1r, R., Makleit, S., and Valovics, G. (1976). Pharmaceutical Composition Having Synergistic Analgesic Activity and Containing Azidomorphine or Azidocodeine, Chinoin Pharmaceutical and Chemical Works Ltd.: Budapest, Hungary. (4,035,491), U.S. Patent."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1111\/j.2042-7158.1973.tb09982.x","article-title":"The pharmacology of azidomorphine and azidocodeine","volume":"25","author":"Knoll","year":"1973","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1007\/BF00798887","article-title":"Effect of morphine and azidomorphine on cortical unit activity","volume":"83","author":"Bulaev","year":"1977","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/BF00806154","article-title":"Pharmacology of azidomorphine","volume":"85","author":"Bulaev","year":"1978","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_181","first-page":"501","article-title":"The metabolism of azidomorphine in the rat","volume":"53","author":"Knoll","year":"1975","journal-title":"Med. Biol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1159\/000136457","article-title":"Kinetic parameters of a new narcotic agonist, azidomorphine","volume":"10","author":"Knoll","year":"1973","journal-title":"Pharmacology"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1007\/BF00965775","article-title":"Azidomorphine is an agonist of high-affinity opioid receptor binding sites","volume":"11","author":"Wollemann","year":"1986","journal-title":"Neurochem. Res."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.2042-7158.1975.tb09416.x","article-title":"The pharmacology of 14-hydroxy-azidomorphine","volume":"27","author":"Knoll","year":"1974","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3109\/00498257809060954","article-title":"The metabolism of azidomorphine in a human subject","volume":"8","author":"Cone","year":"1978","journal-title":"Xenobiotica"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1107\/S056774087400344X","article-title":"The crystal and molecular structure of 6-deoxy-6-azidodihydroisomorphine, C17H20N4O2","volume":"30","author":"Simon","year":"1974","journal-title":"Acta Cryst. B"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1107\/S0567740876008479","article-title":"The crystal and molecular structure of 6-deoxy-6-azido-14-hydroxydihydroisomorphine, C17H20N4O3","volume":"32","author":"Simon","year":"1976","journal-title":"Acta Cryst. B"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/oms.1210090904","article-title":"Mass spectrometric studies on azidomorphine derivatives","volume":"9","author":"Makleit","year":"1974","journal-title":"Org. Mass Spectrom."},{"key":"ref_189","first-page":"265","article-title":"A morfinsz\u00e1rmaz\u00e9kok C-gy\u0171r\u0171j\u00e9nek t\u00e9rszerkezeti adotts\u00e1gai \u00e9s az infrav\u00f6r\u00f6s spektrumaik k\u00f6z\u00f6tti \u00f6sszef\u00fcgg\u00e9sek vizsg\u00e1lata","volume":"77","author":"Dinya","year":"1971","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_190","first-page":"141","article-title":"A morfinsz\u00e1rmaz\u00e9kok elektron \u00e9s t\u00e9rszerkezet\u00e9nek vizsg\u00e1lata \u00e9s \u00f6sszef\u00fcgg\u00e9s\u00fck a farmakol\u00f3giai hat\u00e1ssal","volume":"39","author":"Dinya","year":"1973","journal-title":"K\u00e9m. K\u00f6zl."},{"key":"ref_191","first-page":"125","article-title":"Quantum-chemical calculations for morphine alkaloids","volume":"71","author":"Dinya","year":"1972","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_192","first-page":"430","article-title":"Tozil-, ill. mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XVII. \u201cAzidomorfin\u201d -sz\u00e1rmaz\u00e9kok, I","volume":"82","author":"Makleit","year":"1976","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_193","first-page":"165","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, XVII. \u201cAzidomorphine\u201d derivatives I","volume":"93","author":"Makleit","year":"1977","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_194","unstructured":"Bogn\u00e1r, R., Makleit, S., Kiss, G., Ber\u00e9nyi, S., Mile, T., Knoll, J., Elek, S., Gy\u00f6k\u00e9r, I., Zoltai, A., and T\u00f3th, G. (1977). 6-Deoxy-6-Azido-14-Hydroxy-7,8-Dihydro Isomorphine or a Pharmacetuically Acceptable Salt Thereof. (4,144,236), US Patent."},{"key":"ref_195","first-page":"1","article-title":"Tozil-, illetve mezilsz\u00e1rmaz\u00e9kok reakci\u00f3inak vizsg\u00e1lata a morfinsorban, XIII. Morfin-alkaloidok azidosz\u00e1rmaz\u00e9kai","volume":"44","author":"Makleit","year":"1975","journal-title":"K\u00e9m. K\u00f6zl."},{"key":"ref_196","first-page":"203","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group. XIII. Azido derivatives of morphine alkaloids","volume":"8","author":"Makleit","year":"1975","journal-title":"Bulg. Chem. Commun."},{"key":"ref_197","first-page":"432","article-title":"Tozil-, ill. mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XVIII. \u201cAzidomorfin\u201d-sz\u00e1rmaz\u00e9kok II","volume":"82","author":"Makleit","year":"1976","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_198","first-page":"169","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, XVIII. \u201cAzidomorphine\u201d derivatives, II","volume":"93","author":"Makleit","year":"1977","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/00304947409355125","article-title":"Hydroxyl group elimination in the morphine series","volume":"6","author":"Kerekes","year":"1974","journal-title":"Org. Prep. Proced. Int."},{"key":"ref_200","first-page":"190","article-title":"Tozil-, illetve mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XX. A mezil\u00e9szterek el\u0151\u00e1ll\u00edt\u00e1s\u00e1r\u00f3l","volume":"83","author":"Makleit","year":"1977","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_201","first-page":"161","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, XX. Synthesis of mesyl esters","volume":"94","author":"Makleit","year":"1977","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_202","first-page":"241","article-title":"Circulatory, respiratory and antitussive effects of azidomorphine and related substances","volume":"210","author":"Knoll","year":"1974","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_203","unstructured":"Bogn\u00e1r, R., Makleit, S., Kiss, G., Ber\u00e9nyi, S., Mile, T., Knoll, J., Elek, S., Gy\u00f6k\u00e9r, I., Zoltai, A., and T\u00f3th, G. (1978). 7,8-Dihydroisomorphine derivative, namely azidoethylmorphine. (4,167,636), U.S. Patent."},{"key":"ref_204","first-page":"434","article-title":"Tozil-, ill. mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XIX. \u201cAzidomorfin\u201d-sz\u00e1rmaz\u00e9kok","volume":"82","author":"Makleit","year":"1976","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_205","first-page":"175","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, XIX. \u201cAzidomorphine\u201d derivatives III","volume":"93","author":"Makleit","year":"1977","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_206","first-page":"268","article-title":"The pharmacology of N-substituted azidomorphines","volume":"228","author":"Knoll","year":"1977","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_207","first-page":"627","article-title":"Azidomorphines and heterogenous opiate receptors","volume":"40","author":"Wagner","year":"1988","journal-title":"Pol. J. Pharmacol. Pharm."},{"key":"ref_208","unstructured":"Holaday, J.W., Law, P.-Y., and Herz, A. (1986). Comparison of the opioid activity of CAM and \u03ba agonists, NIDA Research Monograph 75, Proceedings of the 1986 INRC Progress in Opioid Research, International Narcotics Research Conference, San Francisco, CA, USA, 6\u201311 July 1986."},{"key":"ref_209","unstructured":"Knoll, J., Makleit, S., Ber\u00e9nyi, S., Hosztafi, S., F\u00fcrst, S., Knoll, B., Kiss, G., and Gyulai, Z. (1985). Elj\u00e1r\u00e1s N-Szubsztitu\u00e1lt-N-Demetil-Azidoetilmorfin-Sz\u00e1rmaz\u00e9kok El\u0151\u00e1ll\u00edt\u00e1s\u00e1ra. (199,843), Hungarian Patent."},{"key":"ref_210","first-page":"508","article-title":"Morfinv\u00e1zas alkaloidok \u00faj epoxisz\u00e1rmaz\u00e9kainak el\u0151\u00e1ll\u00edt\u00e1sa \u00e9s \u00e1talak\u00edt\u00e1sai","volume":"92","author":"Makleit","year":"1986","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_211","first-page":"255","article-title":"Morphine alkaloids, 104. Synthesis and conversions of new epoxy derivatives","volume":"125","author":"Makleit","year":"1988","journal-title":"Acta. Chim. Hung."},{"key":"ref_212","first-page":"517","article-title":"A 8\u03b2,14\u03b2-epoxi-kodid reakci\u00f3inak tanulm\u00e1nyoz\u00e1sa","volume":"94","author":"Makleit","year":"1988","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_213","first-page":"99","article-title":"Investigation of the reactions of 8,14\u03b2-epoxycodide","volume":"127","author":"Makleit","year":"1990","journal-title":"Acta Chim. Hung."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1248\/cpb.17.1549","article-title":"Studies on the morphine alkaloids and its related compounds. XV. Isolations of 8\u03b2,14\u03b2-epoxy-codide and 14-hydroxy-dihydropseudocodeine from some nucleophilic substitution reaction products of tosylate of 14-hydroxy-codeine or its isomers","volume":"17","author":"Seki","year":"1969","journal-title":"Chem. Pharm. Bull."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1248\/cpb.17.1555","article-title":"Studies on the morphine alkaloids and its related compounds. XVI. Synthesis of 14-hydroxy-allopseudocodeine 8-ethers and its derivatives","volume":"17","author":"Seki","year":"1969","journal-title":"Chem. Pharm. Bull."},{"key":"ref_216","first-page":"228","article-title":"Tozil, illetve mezilsz\u00e1rmaz\u00e9kok reakci\u00f3inak vizsg\u00e1lata a morfinsorban, XI.: 14-Hidroxi-morfin-sz\u00e1rmaz\u00e9kok, II. Halog\u00e9nvegy\u00fcletek","volume":"78","author":"Makleit","year":"1972","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_217","first-page":"111","article-title":"Conversions of tosyl and mesyl derivatives of morphine group. XI.: 14-Hydroxymorphine derivatives. II. Halogen compounds","volume":"74","author":"Makleit","year":"1972","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1021\/ja00989a030","article-title":"Novel analgesics and molecular rearrangements in the morphine-thebaine group I. Ketones derived from 6,14-endo-ethenotetrahydrtothebaine","volume":"89","author":"Bentley","year":"1967","journal-title":"J. Am. Chem. Soc."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/bscb.19890980405","article-title":"Face selectivity of the Diels-Alder reaction of thebaine-like morphinandienes, A computational approach (Chemistry of opium alkaloids, Part XXXI)","volume":"98","author":"Linders","year":"1989","journal-title":"Bull. Soc. Chim. Belg."},{"key":"ref_220","unstructured":"Pham, P.T.K., and Rice, K.C. (1990). Novel thebainelike morphinan-dienes and their Diels-Alder adducts, NIDA Research Monograph Series, Drugs of Abuse: Chemistry, Pharmacology, Immunology, and AIDS."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"717","DOI":"10.2174\/1381612043453027","article-title":"The orvinols and related opioids\u2014High affinity ligands with diverse efficacy profiles","volume":"10","author":"Lewis","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_222","first-page":"1139","article-title":"Steric factors in the azidolysis\u2013thermolysis of some 5-tosyloxymethylbicyclo [2.2.2] oct-2-enes to yield 4-azatetracyclo [4.4.0.02.4.03.8]decanes","volume":"1","author":"Batta","year":"1991","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/00304949109458290","article-title":"Synthesis of a new azatetracyclodecane ring system via intramolecular addition of azide on double bond","volume":"23","author":"Batta","year":"1991","journal-title":"Org. Prep. Proced. Int."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/mrc.1260301318","article-title":"C-19 Configurational assignments in some morphine derivatives by homonuclear NOE","volume":"30","author":"Batta","year":"1992","journal-title":"Magn. Reson. Chem."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/ardp.19933260602","article-title":"Morphine Alkaloids, CXVII: Investigation of the azidolysis of tertiary alcohols of thebaine derivatives with bridged ring C","volume":"326","author":"Sepsi","year":"1993","journal-title":"Arch. Pharm."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1016\/S0040-4020(01)97101-7","article-title":"Alcaloides steroidiques\u2014CLXVII: Synthese d\u2019azides tertiaires en serie alicyclique\u2014III","volume":"30","author":"Pancrazi","year":"1974","journal-title":"Tetrahedron"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/jps.2600730225","article-title":"Stability of the 6,14-endo-ethanotetrahydrooripavine analgesics: Acid-catalyzed rearrangement of buprenorphine","volume":"73","author":"Cone","year":"1984","journal-title":"J. Pharm. Sci."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S0960-894X(99)00085-2","article-title":"Ring constrained analogues of the orvinols: The furanomorphides","volume":"9","author":"Husbands","year":"1999","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/BF00807259","article-title":"Syntheses and transformations of novel nitrogen and sulfur containing morphinandienes","volume":"128","author":"Makleit","year":"1997","journal-title":"Monatsh. Chem."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1021\/ja01588a033","article-title":"The synthesis of morphine","volume":"78","author":"Gates","year":"1956","journal-title":"J. Am. Chem. Soc."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1021\/ja00880a031","article-title":"The closure of the oxide bridge in the morphine series","volume":"84","author":"Gates","year":"1962","journal-title":"J. Am. Chem. Soc."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1021\/jm00232a001","article-title":"Practical synthesis of codeine from dihydrothebainone","volume":"19","author":"Weller","year":"1976","journal-title":"J. Med. Chem."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1021\/jo01303a045","article-title":"Synthetic opium alkaloids and derivatives. A short total synthesis of (\u00b1)-dihydrothebainone, (\u00b1)-dihydrocodeinone, and (\u00b1)-nordihydrocodeinone as an approach to a practical synthesis of morphine, codeine and congeners","volume":"45","author":"Rice","year":"1980","journal-title":"J. Org. Chem."},{"key":"ref_234","first-page":"7461","article-title":"Tritiated opioid receptor ligands as radiotracers","volume":"19","author":"Mallareddy","year":"2013","journal-title":"Curr. Pharm. Design"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/jlcr.3094","article-title":"Morphinan alkaloids labeled with tritium: Synthesis and applications","volume":"56","author":"Filer","year":"2013","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"8315","DOI":"10.1021\/acs.jmedchem.5b00258","article-title":"Applications of fluorine in medicinal chemistry","volume":"58","author":"Gillis","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.1039\/D0OB00619J","article-title":"Fluorinated and [18F]fluorinated morphinan based opioid ligands","volume":"18","author":"Sandulenko","year":"2020","journal-title":"Org. Biomol. Chem."},{"key":"ref_238","first-page":"282","article-title":"Synthesis and chemical transformation of halogen-containing morphine derivatives","volume":"52","author":"Makleit","year":"1997","journal-title":"Magy. K\u00e9m. Lapja"},{"key":"ref_239","first-page":"327","article-title":"Tozil-, illetve mezilsz\u00e1rmaz\u00e9kok vizsg\u00e1lata a morfinsorban, XXI. A dihidrokodein C-6-halog\u00e9nsz\u00e1rmaz\u00e9kai","volume":"83","author":"Somogyi","year":"1977","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_240","first-page":"339","article-title":"Conversions of tosyl and mesyl derivatives of the morphine group, XXI. C-6 Halogen derivatives of dihydrocodeine","volume":"97","author":"Somogyi","year":"1978","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_241","unstructured":"Boswell, G.A., and Henderson, R.M. (1979). Fluoro Analogs of Hydrocodone and Oxycodone Useful as Analgesics, Narcotic Antagonists or Both. (4,241,065), U.S. Patent."},{"key":"ref_242","unstructured":"Ganti, V. (1982). Analgesic, Antagonist, and\/or Anorectic 14-Fluoromorphinans. (4,451,470), US Patent."},{"key":"ref_243","unstructured":"Rice, K.C., Pert, C.B., Burke, T.R., Larson, S.M., Eckelman, W.C., and Channing, M.A. (1984). Synthesis and Utilization of 17-methyl and 17-cyclopropylmethyl-3,14-dihydroxy-4,5\u03b1-epoxy-6\u03b2-fluoromorphinans (foxy and cyclofoxy) as 18F-Labeled Opioid Ligands for Positron Emission Transaxial Tomography (PETT). (4,775,759), U.S. Patent."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3987\/R-1985-01-0099","article-title":"Probes for narcotic receptor mediated phenomena. 11. Synthesis of 17-methyl and 17-cycloporopylmethyl-3,14-dihydroxy-4,5\u03b1-epoxy-6\u03b2-fluoromorphinans (foxy and cyclofoxy) as a model of opioid ligands suitable for positron emission transaxial tomography","volume":"23","author":"Burke","year":"1985","journal-title":"Heterocycles"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0014-5793(84)81300-9","article-title":"S-[18F]Acetylcyclofoxy: A useful probe for the visualization of opiate receptors in living animals","volume":"177","author":"Pert","year":"1984","journal-title":"FEBS Letters"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/0020-708X(85)90204-2","article-title":"Radiosynthesis of (S)[18F]F-3-acetylcyclofoxy: A high affinity opiate antagonist","volume":"36","author":"Channing","year":"1985","journal-title":"Int. J. Appl. Radiat. Isot."},{"key":"ref_247","unstructured":"Newman, A., Channing, M., Finn, R., Dunn, B., Simpson, N., Carson, R., Ostrowski, N., Cohen, R., Burke, T., and Larson, S. (1988). Ligands for Imaging Opioid Receptors in Conscious Humans by Positron Emission Tomography (PET), NIDA Research Monograph, Problems of Drug Dependence."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/S0022-3565(24)39007-X","article-title":"Opioid receptor imaging with positron emission tomography and [18F]cyclofoxy in long-term, methadone-treated former heroin addicts","volume":"295","author":"Kling","year":"2000","journal-title":"J. Pharm. Exp. Ther."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/recl.19931120207","article-title":"Synthesis and biological activity of new etorphine analogues from 7-chloro-6-demethoxythebaine and 7-chloro-5\u03b2-methyl-6-demethoxythebaine (Chemistry of Opium Alkaloids, part XXXVII)","volume":"112","author":"Woudenberg","year":"1993","journal-title":"Recl. Trav. Chim. Pays-Bas"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0968-0896(98)00267-3","article-title":"Chemistry of opium alkaloids. Part 44: Synthesis and opioid receptor binding profile of substituted ethenoisomorphinans and ethenomorphinans","volume":"7","author":"Maat","year":"1999","journal-title":"Bioorg. Med. Chem."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/0040-4020(95)01066-1","article-title":"Reaction of morphinan-6, 8-dienes with azadienophiles","volume":"52","author":"Marton","year":"1996","journal-title":"Tetrahedron"},{"key":"ref_252","first-page":"178","article-title":"Unexpected effect of fluorine in Diels-Alder reaction of 2-fluoroacrolein with thebaine","volume":"11","author":"Jeong","year":"1990","journal-title":"Bull. Korean Chem. Soc."},{"key":"ref_253","first-page":"258","article-title":"Reaction of thebaine with trifluoromethyl substituted acetylenic dienophiles","volume":"11","author":"Jeong","year":"1990","journal-title":"Bull. Korean Chem. Soc."},{"key":"ref_254","first-page":"257","article-title":"Synthesis of fluorinated new thebaine derivatives as analgesics","volume":"42","author":"Kim","year":"1998","journal-title":"Yakhak Hoechi"},{"key":"ref_255","first-page":"2693","article-title":"A new efficient method for the preparation of 2-fluoro-N-propyl-norapomorphine","volume":"1","author":"Hosztafi","year":"1992","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"409","DOI":"10.2174\/157017807781467560","article-title":"Investigation of the acid-catalyzed rearrangement of morphinans","volume":"4","author":"Neumeyer","year":"2007","journal-title":"Lett. Org. Chem."},{"key":"ref_257","first-page":"26","article-title":"Synthesis and biological evaluation of some halogenated 6,14-ethenomorphinan derivatives","volume":"5","author":"Sepsi","year":"1995","journal-title":"Med. Chem. Res."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s12272-013-0072-z","article-title":"A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats","volume":"36","author":"Srebro","year":"2013","journal-title":"Arch. Pharm. Res."},{"key":"ref_259","unstructured":"Magnus, P., and Ghavimi-Alagha, B. (2012). Chemical Transformations of (-)-Codeine to Afford Derivatives Codeine and Morphine Thereof. (2013\/184,902), WO."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1021\/jm00126a009","article-title":"2-Haloaporphines as potent dopamine agonists","volume":"32","author":"Ramsby","year":"1989","journal-title":"J. Med. Chem."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0028-3908(91)90049-H","article-title":"R-(-)-2-Fluoro-N-n-propylnorapomorphine: A very potent and D2-selective dopamine agonist","volume":"30","author":"Baldessarini","year":"1991","journal-title":"Neuropharmacology"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1080\/00397919408011316","article-title":"Synthesis of new morphine derivatives containing halogen in the aromatic ring","volume":"24","author":"Hosztafi","year":"1994","journal-title":"Synth. Commun."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1080\/00397919608003811","article-title":"Synthesis of new apomorphine derivatives containing halogen (CI and Br) in ring-D","volume":"26","author":"Hosztafi","year":"1996","journal-title":"Synth. Commun."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1021\/jo01307a040","article-title":"Preparation of (-)-[8,9-3H]apomorphine at high specific activity","volume":"45","author":"Filer","year":"1980","journal-title":"J. Org. Chem."},{"key":"ref_265","unstructured":"Filer, C.N. (2005). Radiopharmaceutical and Methods of Synthesis and Use Thereof. (7,323,566), US. Patent."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1007\/BF01919684","article-title":"The analgesic action of 1-fluorocodeine","volume":"30","author":"Lousberg","year":"1974","journal-title":"Experientia"},{"key":"ref_267","first-page":"447","article-title":"A gram scale preparation of 1-fluorocodeine and 1-fluorodihydrocodeine","volume":"137","author":"Makleit","year":"2000","journal-title":"ACH-Models Chem."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1515\/chempap-2016-0033","article-title":"Synthesis of 1-fluoro-substituted codeine derivatives","volume":"70","author":"Hosztafi","year":"2016","journal-title":"Chem. Pap."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.2174\/1570178615666171222163442","article-title":"Synthesis of 1-Iodo-substituted codeine derivatives","volume":"15","author":"Hosztafi","year":"2018","journal-title":"Lett. Org. Chem."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1002\/slct.201600233","article-title":"21,21,21-Trifluorothevinone: The straightest way to fluorinated thevinols and orvinols","volume":"1","author":"Sandulenko","year":"2016","journal-title":"ChemistrySelect"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"9091","DOI":"10.1039\/D3OB01577G","article-title":"C (21)-Di-and monofluorinated scaffold for thevinol\/orvinol-based opioid receptor ligands","volume":"21","author":"Zelentsova","year":"2023","journal-title":"Org. Biomol. Chem."},{"key":"ref_272","first-page":"32","article-title":"Synthesis of aryl-21,21,21-triflurothevinols","volume":"32","author":"Zelentsova","year":"2018","journal-title":"Adv. Chem. Chemical Technol. (Uspekhi V Khimii I Khimicheskoi Tekhnologii)"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.mencom.2022.01.031","article-title":"19F NMR determination of the C20 absolute configuration of C21-fluorinated arylthevinols","volume":"32","author":"Zelentsova","year":"2022","journal-title":"Mendeleev Commun."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"115296","DOI":"10.1016\/j.ejmech.2023.115296","article-title":"C (21)-fluorinated thevinol scaffold for opioid ligands. 21, 21, 21-Trifluoro-6-O-nororvinols: Design, synthesis and analgesic activity","volume":"252","author":"Sandulenko","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"112145","DOI":"10.1016\/j.ejmech.2020.112145","article-title":"Synthesis, biochemical, pharmacological characterization and in silico profile modelling of highly potent opioid orvinol and thevinol derivatives","volume":"191","author":"Marton","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/BF00813809","article-title":"Herstellung von 6, 14-Ethenomorphinan-derivaten","volume":"125","author":"Marton","year":"1994","journal-title":"Monatsh. Chem."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1039\/D2OB02144G","article-title":"Control of the diastereoselectivity at C (20) in the formation of C (21)-fluorinated thevinols","volume":"21","author":"Sandulenko","year":"2023","journal-title":"Org. Biomol. Chem."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1021\/ja00989a031","article-title":"Novel analgesics and molecular rearrangements in the morphine-thebaine group. II. Alcohols derived from 6, 14-endo-etheno-and 6, 14-endo-ethanotetrahydrothebaine","volume":"89","author":"Bentley","year":"1967","journal-title":"J. Am. Chem. Soc."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"4049","DOI":"10.1021\/jm401964y","article-title":"Selectively promiscuous opioid ligands: Discovery of high affinity\/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity","volume":"57","author":"Kumar","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_280","doi-asserted-by":"crossref","unstructured":"Husbands, S.M. (2013). Buprenorphine and related orvinols. Research and Development of Opioid-Related Ligands, American Chemical Society.","DOI":"10.1021\/bk-2013-1131.ch007"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1007\/s11172-022-3705-x","article-title":"Thevinoic acid fluoroalkyl esters","volume":"71","author":"Sandulenko","year":"2022","journal-title":"Russ Chem. Bull."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"110189","DOI":"10.1016\/j.jfluchem.2023.110189","article-title":"A straightforward trifluoromethylation at the C6 position of morphinane alkaloids, their modification and evaluation of inhibition of the SARS-CoV-2 main protease","volume":"271","author":"Finke","year":"2023","journal-title":"J. Fluor. Chem."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1246\/bcsj.40.2380","article-title":"Preparation of esters of carboxylic and phosphoric acid via quaternary phosphonium salts","volume":"40","author":"Mitsunobu","year":"1967","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-1981-29317","article-title":"The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products","volume":"1","author":"Mitsunobu","year":"1981","journal-title":"Synthesis"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1039\/C5QO00016E","article-title":"The Mitsunobu reaction in the 21st century","volume":"2","author":"Fletcher","year":"2015","journal-title":"Org. Chem. Front."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/jhet.5570340201","article-title":"Application of the Mitsunobu reaction in the field of alkaloids","volume":"34","author":"Simon","year":"1997","journal-title":"J. Heterocycl. Chem."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1098\/rspb.1979.0076","article-title":"Specific protection of the binding sites of D-Ala2-D-Leu5-enkephalin (\u03b4-receptors) and dihydromorphine (\u03bc-receptors)","volume":"205","author":"Robson","year":"1979","journal-title":"Proc. Royal Soc. Lond. B. Biol. Sci."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1073\/pnas.77.1.281","article-title":"Selective protection of stereospecific enkephalin and opiate binding against inactivation by N-ethylmaleimide: Evidence for two classes of opiate receptors","volume":"71","author":"Smith","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"13434","DOI":"10.1016\/S0021-9258(19)76445-X","article-title":"Affinity labeling of \u03b4-opiate receptors using [D-Ala2, Leu5, Cys6] enkephalin. Covalent attachment via thiol-disulfide exchange","volume":"262","author":"Bowen","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1248\/cpb.36.2282","article-title":"Design and synthesis of sulfur-containing morphine and an opioid receptor probe","volume":"36","author":"Fujii","year":"1988","journal-title":"Chem. Pharm. Bull."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1248\/cpb.12.104","article-title":"Studies on Morphine Alkaloids. I. Nuclear magnetic resonance spectral studies on morphine alkaloids. I","volume":"12","author":"Okuda","year":"1964","journal-title":"Chem. Pharm. Bull."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1248\/cpb.38.1438","article-title":"Design synthesis of an opioid receptor probe: Mode of binding of S-Activated (-)-6-\u03b2-sulfhydryldihydromorphine with the SH group in the mu-opioid receptor","volume":"38","author":"Kanematsu","year":"1990","journal-title":"Chem. Pharm. Bull."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1248\/cpb.38.1441","article-title":"Molecular srtucture of (-)-3-acetyl-6-beta-(acetylthio)-N-(cyclopropylmethyl) normorphine and its 14-hydroxy congeners","volume":"38","author":"Kanematsu","year":"1990","journal-title":"Chem. Pharm. Bull."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1002\/cber.19801131218","article-title":"Claisen-Reaktionen an Codeinen. 8-Alkyl-8, 14-dihydro-6-desmethoxythebaine und-oripavine","volume":"113","author":"Fleischhacker","year":"1980","journal-title":"Chem. Ber."},{"key":"ref_295","doi-asserted-by":"crossref","unstructured":"Kirby, G.W., and Massey, S.R. (1971). An efficient preparation of isocodeine from codeine. J. Chem. Soc. C, 3047\u20133048.","DOI":"10.1039\/j39710003047"},{"key":"ref_296","unstructured":"Simon, C. (1993). A Mitsunobu-Reakci\u00f3 Alkalmaz\u00e1sa a Morfin-Alkaloidok K\u00f6r\u00e9ben. [C.Sc. Dissertation, Kossuth Lajos Tudom\u00e1nyegyetem Debrecen]."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/00397919108016763","article-title":"Application of the Mitsunobu reaction for the preparation of isomorphine and isocodeine derivatives","volume":"21","author":"Simon","year":"1991","journal-title":"Synth. Commun."},{"key":"ref_298","first-page":"16","article-title":"Influence of spatial orientation of the C-6-OH group in ring C of morphine derivatives on opioid activity","volume":"328","author":"Friedmann","year":"1994","journal-title":"Arch. Int. Pharmacodyn. Th\u00e9r."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1080\/00397917908064183","article-title":"Synthesis of 6\u03b2-Halogenodeoxyneopine from Neopine","volume":"9","author":"Maat","year":"1979","journal-title":"Synth. Commun."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1021\/jm00218a023","article-title":"Stereochemical studies on medicinal agents. 23. Synthesis and biological evaluation of 6-amino derivatives of naloxone and naltrexone","volume":"20","author":"Jiang","year":"1977","journal-title":"J. Med. Chem."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"3366","DOI":"10.1021\/jo01304a051","article-title":"Stereospecific synthesis of the 6\u03b1- and 6\u03b2-amino derivatives of naltrexone and oxymorphone","volume":"45","author":"Sayre","year":"1980","journal-title":"J. Org. Chem."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1021\/jo00351a025","article-title":"Stereoselectivity of the reduction of naltrexone oxime with borane","volume":"51","author":"Mohamed","year":"1986","journal-title":"J. Org. Chem."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1080\/00397919208020855","article-title":"Application of the Mitsunobu reaction for morphine compounds. Preparation of 6\u03b2-aminomorphine and codeine derivatives. Morphine Alkaloids Part 115","volume":"22","author":"Simon","year":"1992","journal-title":"Synth. Commun."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.3987\/COM-94-6691","article-title":"Applicaltion of the Mitsunobu reaction in the morphine series. Preparation of 6\u03b2-amino-14\u03b2-hydroxymorphine and 14-hydroxycodeine derivatives","volume":"38","author":"Simon","year":"1994","journal-title":"Heterocycles"},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"9757","DOI":"10.1016\/S0040-4020(01)85541-1","article-title":"Stereoselective synthesis of \u03b2-naltrexol, \u03b2-naloxol \u03b2-naloxamine, \u03b2-naltrexamine and related compounds by the application of the Mitsunobu reaction","volume":"50","author":"Simon","year":"1994","journal-title":"Tetrahedron"},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/mrc.1260300617","article-title":"Substituent-dependent conformational changes in 6\u03b2-substituted codeine derivatives","volume":"30","author":"Makleit","year":"1992","journal-title":"Magn. Reson. Chem."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3727\/107156995819563889","article-title":"Structure-activity relationships of N-cyclopropylmethyl morphine derivatives in isolated organs","volume":"1","author":"Riba","year":"1995","journal-title":"Analgesia"},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1248\/cpb.17.1847","article-title":"Studies on Morphine Alkaloids. V. Reaction Mechanism of the Reduction of 14\u03b2-Bromocodeinone with Sodium Borohydride","volume":"17","author":"Abe","year":"1969","journal-title":"Chem. Pharm. Bull."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"6475","DOI":"10.1016\/0040-4039(93)85074-7","article-title":"Application of the Mitsunobu reaction in the morphine series: The reaction of 14\u03b2-chloro and 14\u03b2-bromocodeine with phthalimide and diphenylphosphoryl azide","volume":"34","author":"Simon","year":"1993","journal-title":"Tetrahedron Lett."},{"key":"ref_310","first-page":"2734","article-title":"The first preparation of 6\u03b2-bromo codeine and morphine derivatives. Kinetic vs. thermodynamic control","volume":"12","author":"Simon","year":"1997","journal-title":"J. Chem. Res."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1124\/jpet.114.214031","article-title":"Characteristics of TRK-130 (Naltalimide), a novel opioid ligand, as a new therapeutic agent for overactive bladder","volume":"350","author":"Fujimura","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_312","unstructured":"Izumimoto, N., Kawai, K., Kawamura, K., Fujimura, M., and Komagata, T. (2003). Remedies or Preventives for Urinary Frequency or Urinary Incontinence and Morphinan Derivatives Having Nitrogen-Containing Heterocyclic Group. (7,320,984), U.S. Patent."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.vaccine.2014.01.028","article-title":"Facial recognition of heroin vaccine opiates: Type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine","volume":"32","author":"Matyas","year":"2014","journal-title":"Vaccine"},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1021\/acs.bioconjchem.5b00085","article-title":"Efficacy, but not antibody titer or affinity, of a heroin hapten conjugate vaccine correlates with increasing hapten densities on tetanus toxoid, but not on CRM197 carriers","volume":"26","author":"Jalah","year":"2015","journal-title":"Bioconjugate Chem."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1021\/acs.jmedchem.7b01811","article-title":"Fluorescently labeled morphine derivatives for bioimaging studies","volume":"61","author":"Lam","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1248\/cpb.46.366","article-title":"Discovery of a structurally novel opioid \u03ba-agonist derived from 4,5-epoxymorphinan","volume":"46","author":"Nagase","year":"1998","journal-title":"Chem. Pharm. Bull."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1124\/jpet.104.073668","article-title":"Comparison of pharmacological activities of three distinct \u03ba ligands (Salvinorin A, TRK-820 and 3FLB) on \u03ba opioid receptors in vitro and their antipruritic and antinociceptive activities in vivo","volume":"312","author":"Wang","year":"2005","journal-title":"J. Pharm. Exp. Ther."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1016\/j.bmcl.2017.06.017","article-title":"Discovery of highly selective \u03ba-opioid receptor agonists: 10\u03b1-Hydroxy TRK-820 derivatives","volume":"27","author":"Suzuki","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.ejmech.2013.09.031","article-title":"Novel 6\u03b2-acylaminomorphinans with analgesic activity","volume":"69","author":"Hosztafi","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1039\/C6MD00450D","article-title":"Synthesis and pharmacological evaluation of novel selective MOR agonist 6\u03b2-pyridinyl amidomorphines exhibiting long-lasting antinociception","volume":"8","author":"Urai","year":"2017","journal-title":"MedChemComm"},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2174\/138161207779313821","article-title":"PET and SPECT imaging of the opioid system: Receptors, radioligands and avenues for drug discovery and development","volume":"13","author":"Lever","year":"2007","journal-title":"Curr. Pharm. Design"},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1093\/brain\/awm255","article-title":"Imaging of opioid receptors in the central nervous system","volume":"131","author":"Henriksen","year":"2008","journal-title":"Brain"},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jlcr.3005","article-title":"Positron emission tomography radioligands for the opioid system","volume":"56","author":"Dannals","year":"2013","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0020-708X(85)90089-4","article-title":"Radiosynthesis of an opiate receptor binding radiotracer: [11C]carfentanil","volume":"36","author":"Dannals","year":"1985","journal-title":"Int. J. Appl. Radiat. Isot."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.2174\/092986709788803295","article-title":"Recent developments in the chemistry of thebaine and its transformation products as pharmacological targets","volume":"16","author":"Sipos","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/jlcr.2580360206","article-title":"Synthesis of N1\u2032-([11C]methyl)naltrindole ([11C]MeNTI): A radioligand for positron emission tomographic studies of delta opioid receptors","volume":"36","author":"Lever","year":"1995","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/(SICI)1099-1344(199901)42:1<43::AID-JLCR165>3.0.CO;2-2","article-title":"Synthesis of N1\u2032-([18F]fluoroethyl)naltrindole ([18F]FEtNTI): A radioligand for positron emission tomographic studies of delta opioid receptors","volume":"42","author":"Mathews","year":"1999","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1016\/j.bmcl.2011.05.008","article-title":"Generation of novel radiolabeled opiates through siete-selective iodination","volume":"21","author":"Majumdar","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_329","unstructured":"Manske, R.H.F. (1971). The morphine alkaloids. The Alkaloids: Chemistry and Physiology, Academic Press Inc."},{"key":"ref_330","doi-asserted-by":"crossref","first-page":"6774","DOI":"10.1021\/jo961473k","article-title":"Direct and simple O-demethylation of thebaine to oripavine","volume":"61","author":"Coop","year":"1996","journal-title":"J. Org. Chem."},{"key":"ref_331","doi-asserted-by":"crossref","first-page":"4392","DOI":"10.1021\/jo9801972","article-title":"L-Selectride as a general reagent for the O-demethylation and N-decarbomethoxylation of opium alkaloids and derivatives","volume":"63","author":"Coop","year":"1998","journal-title":"J. Org. Chem."},{"key":"ref_332","doi-asserted-by":"crossref","first-page":"704","DOI":"10.4236\/abb.2014.58084","article-title":"Recent Advances in the Chemistry of Oripavine and Its Derivatives","volume":"5","author":"Hosztafi","year":"2014","journal-title":"Adv. Biosci. Biotechnol."},{"key":"ref_333","doi-asserted-by":"crossref","first-page":"4015","DOI":"10.1016\/S0040-4039(01)83849-1","article-title":"Synthesis of carbon-11 labeled diprenorphine: A radioligand for positron emission tomographic studies of opiate receptors","volume":"28","author":"Lever","year":"1987","journal-title":"Tetrahedron Lett."},{"key":"ref_334","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/0969-8043(94)90217-8","article-title":"Automated radiosyntheses of [6-O-methyl-11C]diprenorphine and [6-O-methyl-11C]buprenorphine from 3-O-trityl protected precursors","volume":"45","author":"Luthra","year":"1994","journal-title":"Appl. Radiat. Isot."},{"key":"ref_335","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/0883-2889(90)90022-9","article-title":"Facile synthesis of [11C]buprenorphine for positron emission tomographic studies of opioid receptors","volume":"41","author":"Lever","year":"1990","journal-title":"Int. J. Radiat. Appl. Instrum. Part A. Appl. Radiat. Isot."},{"key":"ref_336","doi-asserted-by":"crossref","first-page":"5586","DOI":"10.1021\/jm900892x","article-title":"Synthesis and evaluation of a full-agonist orvinol for PET-Imaging of opioid receptors: [11C]PEO","volume":"52","author":"Marton","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_337","doi-asserted-by":"crossref","first-page":"11554","DOI":"10.3390\/molecules171011554","article-title":"Design and synthesis of an 18F-labeled version of phenylethyl orvinol ([18F]FE-PEO) for PET-imaging of opioid receptors","volume":"17","author":"Marton","year":"2012","journal-title":"Molecules"},{"key":"ref_338","doi-asserted-by":"crossref","first-page":"299","DOI":"10.2967\/jnumed.112.108688","article-title":"Synthesis and evaluation of 18F-FE-PEO in rodents: An 18F-labeled full agonist for opioid receptor imaging","volume":"54","author":"Riss","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_339","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.1021\/jm500503k","article-title":"Synthesis and evaluation of three structurally related 18F-labeled orvinols of different intrinsic activities: 6-O-[18F]Fluoroethyl-diprenorphine ([18F]FDPN), 6-O-[18F]fluoroethyl-buprenorphine ([18F]FBPN), and 6-O-[18F]fluoroethyl-phenethyl-orvinol ([18F]FPEO)","volume":"57","author":"Schoultz","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_340","first-page":"1279","article-title":"6-O-(2-[18F]Fluoroethyl-6-O-desmethyldiprenorphine ([18F]DPN): Synthesis, biologic evaluation, and comparison with [11C]DPN in humans","volume":"41","author":"Wester","year":"2000","journal-title":"J. Nucl. Med."},{"key":"ref_341","doi-asserted-by":"crossref","first-page":"7271","DOI":"10.3390\/molecules18067271","article-title":"A fully automated radiosynthesis of [18F]fluoroethyl-diprenorphine on a single module by use of SPE cartridges for preparation of high quality 2-[18F]fluoroethyl tosylate","volume":"18","author":"Schoultz","year":"2013","journal-title":"Molecules"},{"key":"ref_342","doi-asserted-by":"crossref","first-page":"344","DOI":"10.2174\/1570178617999200719153812","article-title":"A new precursor for the radiosynthesis of 6-O-(2-[18F]fluoroethyl)-6-O-desmethyl-diprenorphine ([18F]FE-DPN) by nucleophilic radiofluorination","volume":"18","author":"Marton","year":"2021","journal-title":"Lett. Org. Chem."},{"key":"ref_343","doi-asserted-by":"crossref","unstructured":"N\u00e9meth, E., Gyuricza, B., Forg\u00e1cs, V., Cumming, P., Henriksen, G., Marton, J., Bauer, B., Mikecz, P., and Fekete, A. (2023). Optimization of a Nucleophilic Two-Step Radiosynthesis of 6-O-(2-[18F]fluoroethyl)-6-O-desmethyl-diprenorphine ([18F] FE-DPN) for PET Imaging of Brain Opioid Receptors. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713152"},{"key":"ref_344","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s11307-022-01767-5","article-title":"6-O-(2-[18F]Fluoroethyl)-6-O-desmethyl-diprenorphine ([18F]FE-DPN) preferentially binds to mu opioid receptors in vivo","volume":"25","author":"Levinstein","year":"2023","journal-title":"Mol. Imag. Biol."},{"key":"ref_345","first-page":"260","article-title":"Vizsg\u00e1latok a morfin szint\u00e9zis\u00e9vel \u00f6sszef\u00fcgg\u00e9sben, II. Az O6-demetil-szalutaridin \u00e1talak\u00edt\u00e1sa szalutaridinn\u00e9","volume":"86","author":"Makleit","year":"1980","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_346","first-page":"37","article-title":"Studies related to the synthesis of morphine, II. Conversion of O6-demethylsalutaridine into salutaridine","volume":"106","author":"Makleit","year":"1981","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_347","first-page":"5","article-title":"Buprenorphine\u2014Background to its development as a treatment for opioid dependence","volume":"Volume 121","author":"Blaine","year":"1992","journal-title":"NIDA Research Monograph 121, Buprenorphine: An Alternative Treatment for Opioid Dependence"},{"key":"ref_348","unstructured":"Ber\u00e9nyi, S., Hosztafi, S., Makleit, S., Simon, C., and Marton, J. (1991). New Process for Producing N-Substituted-6,14-endo-ethanotetrahydrothebaine and -Oripavine Derivatives and Their Salts. (210,158), Hungarian Patent."},{"key":"ref_349","doi-asserted-by":"crossref","unstructured":"Marton, J., Simon, C., Hosztafi, S., Ber\u00e9nyi, S., Makleit, S., Kabai, S., Kolozsi, S., Kov\u00e1cs, Z., and Nagy, I. (1995). New Process for Producing 6,14-ethenomorphinan Derivatives and Salts Thereof. (76,478), Hungarian Patent.","DOI":"10.1007\/BF00813809"},{"key":"ref_350","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1002\/jlac.1993199301144","article-title":"Herstellung von 6,14 Ethenomorphinan-Derivaten","volume":"8","author":"Marton","year":"1993","journal-title":"Liebigs Ann. Chem."},{"key":"ref_351","first-page":"95","article-title":"Invetsigation of biologically active compounds at the Department of Organic Chemistry of University of Debrecen between 1992\u20132009, I","volume":"79","author":"Antus","year":"2009","journal-title":"Acta Pharm. Hung."},{"key":"ref_352","first-page":"15","article-title":"Morfin-alkaloidok N-demetilez\u00e9se. A nor-neopin el\u0151\u00e1ll\u00edt\u00e1sa","volume":"86","author":"Hosztafi","year":"1980","journal-title":"Magy. K\u00e9m. Foly."},{"key":"ref_353","first-page":"371","article-title":"N-Demethylation of morphine alkaloids. Preparation of norneopine","volume":"103","author":"Hosztafi","year":"1980","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_354","first-page":"61","article-title":"Reactions of azodicarboxylic esters with amines","volume":"55","author":"Hosztafi","year":"1987","journal-title":"Sci. Pharm."},{"key":"ref_355","unstructured":"Hosztafi, S. (2020). Morfinv\u00e1z C Gy\u0171r\u0171j\u00e9ben M\u00f3dos\u00edtott Vegy\u00fcletek Szint\u00e9zise. [D.Sc. Dissertation, Semmelweis University]."},{"key":"ref_356","unstructured":"Seller, S., Szab\u00f3, M., Palincza, J., Imre, L., Cseleny\u00e1k, Z., and Tompa, J. (2002). Process for Separation of Opium Alkaloids. (225,038), Hungarian Patent."},{"key":"ref_357","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41380-020-0661-4","article-title":"The changing opioid crisis: Development, challenges and opportunities","volume":"26","author":"Volkow","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_358","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3390\/psychoactives2040020","article-title":"The imperative of regulation: The co-creation of a medical and non-medical US opioid crisis","volume":"2","author":"Pieters","year":"2023","journal-title":"Psychoactives"},{"key":"ref_359","first-page":"93","article-title":"How to Combat the Global Opioid Crisis","volume":"5","author":"Dennen","year":"2023","journal-title":"CPQ Neurol. Psychol."},{"key":"ref_360","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1002\/ejp.2011","article-title":"Trends in opioid utilization in Hungary, 2006\u20132020: A nationwide retrospective study with multiple metrics","volume":"26","author":"Engi","year":"2022","journal-title":"Eur. J. Pain"},{"key":"ref_361","first-page":"548","article-title":"A debreceni m\u00e1kalkaloidkutat\u00e1s 50 \u00e9ve\u201450 years on the Research of Poppy Alkaloids in Debrecen","volume":"54","year":"1999","journal-title":"MKL\u2013Magy. K\u00e9m. Lapja."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2736\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:56:03Z","timestamp":1760028963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":361,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26062736"],"URL":"https:\/\/doi.org\/10.3390\/ijms26062736","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]}}}