{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:50:38Z","timestamp":1790387438398,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T00:00:00Z","timestamp":1581638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deyew Biotech Corporation","award":["-"],"award-info":[{"award-number":["-"]}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["NSC100-2622-M-259-001-CC2"],"award-info":[{"award-number":["NSC100-2622-M-259-001-CC2"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The total synthesis of (\u2212)-antrocin and its enantiomer are presented. Antrocin (\u2212)-1 is an important natural product which acts as an antiproliferative agent in a metastatic breast cancer cell line (IC50: 0.6 \u03bcM). The key features of this synthesis are: (a) selective anti-addition of trimethylsilyl cyanide (TMSCN) to \u03b1,\u03b2-unsaturated ketone; (b) resolution of (\u00b1)-7 using chiral auxiliary L-dimethyl tartrate through formation of cyclic ketal diastereomers followed by simple column chromatography separation and acid hydrolysis; (c) substrate-controlled stereoselective aldol condensation of (+)-12 with monomeric formaldehyde and pyridinium chlorochromate (PCC) oxidation for synthesis of essential lactone core in (\u2212)-14; and (d) non-basic Lombardo olefination of the carbonyl at the final step to yield (\u2212)-antrocin. In addition, (+)-9 cyclic ketal diastereomer was converted to (+)-antrocin with similar reaction sequences.<\/jats:p>","DOI":"10.3390\/molecules25040831","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T05:44:12Z","timestamp":1582695852000},"page":"831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synthesis of Natural (\u2212)-Antrocin and Its Enantiomer via Stereoselective Aldol Reaction"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-0167","authenticated-orcid":false,"given":"Venkatachalam","family":"Angamuthu","sequence":"first","affiliation":[{"name":"Department of Chemistry, Pondicherry University, Puducherry 605014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dar-Fu","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Dong Hwa University, Shoufeng Township, Hualien County 974, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/S0962-4562(03)00078-X","article-title":"Sesquiterpene lactones: A diverse class of compounds found in essential oils possessing antibacterial and antifungal properties","volume":"13","author":"Neerman","year":"2003","journal-title":"Int. J. Aromatherapy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2307\/1219846","article-title":"Cladistic analysis of complex natural products: Developing transformation series from sesquiterpene lactone data","volume":"32","author":"Seaman","year":"1983","journal-title":"Taxon"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1039\/np9910800309","article-title":"The occurrence and biological activity of drimane sesquiterpenoids","volume":"8","author":"Jansen","year":"1991","journal-title":"Nat. Prod. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1749-8546-5-4","article-title":"Quality evaluation of mycelial Antrodia camphorata using high-performance liquid chromatography (HPLC) coupled with diode array detector and mass spectrometry (DAD-MS)","volume":"5","author":"Zhao","year":"2010","journal-title":"Chin. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5007","DOI":"10.1021\/jf063484c","article-title":"Chemical Characterization and Anti-inflammatory Effect of Polysaccharides Fractionated from Submerge-Cultured Antrodia camphorata Mycelia","volume":"55","author":"Chen","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"212641","DOI":"10.1093\/ecam\/nep108","article-title":"Review of Pharmacological Effects of Antrodia camphorata and Its Bioactive Compounds","volume":"2011","author":"Geethangili","year":"2011","journal-title":"Evid Based Complement Alternat. Med."},{"key":"ref_7","unstructured":"Chen, J.C. (2008). King of Ganoderma: Antrodia camphorata in Taiwan, Yuen Chi Jai Book Publishing. [2nd ed.]."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/jccs.199500107","article-title":"Constituents of Antrodia Cinnamomea","volume":"42","author":"Wu","year":"1995","journal-title":"J. Chin. Chem. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1574-6968.2002.tb11110.x","article-title":"Antrodia camphorata polysaccharides exhibit anti-hepatitis B virus effects","volume":"209","author":"Lee","year":"2002","journal-title":"Microbiol. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1016\/j.fct.2008.04.036","article-title":"Antrodia camphorata inhibits proliferation of human breast cancer cells in vitro and in vivo","volume":"46","author":"Hseu","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_11","first-page":"2727","article-title":"Anticancer Effects of Eleven Triterpenoids Derived from Antrodia camphorata","volume":"32","author":"Lee","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.jep.2008.10.039","article-title":"Niuchangchih (Antrodia camphorata) and its potential in treating liver diseases","volume":"121","author":"Ao","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.phymed.2018.09.213","article-title":"Antrocin, a bioactive component from Antrodia cinnamomea, suppresses breast carcinogenesis and stemness via downregulation of \u03b2-catenin\/Notch1\/Akt signaling","volume":"52","author":"Chen","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/0031-9422(95)00025-3","article-title":"A sesquiterpene lactone, phenyl and biphenyl compounds from Antrodia cinnamomea","volume":"39","author":"Cherng","year":"1995","journal-title":"Phytochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1021\/tx100318m","article-title":"Identification of Antrocin from Antrodia camphorata as a Selective and Novel Class of Small Molecule Inhibitor of Akt\/mTOR Signaling in Metastatic Breast Cancer MDA-MB-231 Cells","volume":"24","author":"Rao","year":"2011","journal-title":"Chem. Res. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1021\/np0581263","article-title":"Neuroprotective Diterpenes from the Fruiting Body of Antrodia camphorata","volume":"69","author":"Chen","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1021\/jm970569j","article-title":"In Vitro Platelet-Activating Factor Receptor Binding Inhibitory Activity of Pinusolide Derivatives: A Structure\u2212Activity Study","volume":"41","author":"Han","year":"1998","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/jccs.200300022","article-title":"Cytotoxic Constituents of the Leaves of Calocedrus Formosana","volume":"50","author":"Chiang","year":"2003","journal-title":"J. Chin. Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1158\/1535-7163.MCT-06-0190","article-title":"The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays","volume":"5","author":"Smith","year":"2006","journal-title":"Mol. Cancer. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14944","DOI":"10.1021\/ja206837j","article-title":"Total Syntheses of Drimane-Type Sesquiterpenoids Enabled by a Gold-Catalyzed Tandem Reaction","volume":"133","author":"Shi","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12426","DOI":"10.1039\/C6CC06794H","article-title":"A chiral pool approach for asymmetric syntheses of (\u2212)-antrocin, (+)-asperolide C, and (\u2212)-trans-ozic acid","volume":"52","author":"Li","year":"2016","journal-title":"Chem. Comm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9576","DOI":"10.1021\/acs.joc.7b01600","article-title":"Total Synthesis of (+)-Antrocin and Its Diastereomer and Clarification of the Absolute Stereochemistry of (\u2212)-Antrocin","volume":"82","author":"Huang","year":"2017","journal-title":"J. Org. Chem."},{"key":"ref_23","unstructured":"Tai, D.-F., Angamuthu, V., and Tzeng, Y.-M. (2013). Process for preparing optically active antrocin. (US0096324 A1), U.S. Patent."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1021\/jo00219a040","article-title":"Syntheses of alpha.-, beta.-, and gamma.-substituted carnitines via beta.-keto esters","volume":"50","author":"Hosmer","year":"1985","journal-title":"J. Org. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/00397918508076812","article-title":"Trimethylsilyl-Halide-Mediated Conjugated Addition to Allylic Acetals","volume":"15","author":"Feringa","year":"1985","journal-title":"Syn. Comm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16864","DOI":"10.1021\/ja8071918","article-title":"Enantioselective Synthesis of (+)-Cortistatin A, a Potent and Selective Inhibitor of Endothelial Cell Proliferation","volume":"130","author":"Lee","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1021\/jo00406a032","article-title":"Reactions involving electron transfer. 12. Effects of solvent and substituents upon the ability of lithium diorganocuprates to add to enones","volume":"43","author":"House","year":"1978","journal-title":"J. Org. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1021\/ol025968+","article-title":"Progress toward the Synthesis of Garsubellin A and Related Phloroglucins:\u2009 The Direct Diastereoselective Synthesis of the Bicyclo[3.3.1]nonane Core","volume":"4","author":"Spessard","year":"2002","journal-title":"Org. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4098","DOI":"10.1021\/jo070257g","article-title":"Enantioselective Synthesis of (+)-Majusculone","volume":"72","author":"Taber","year":"2007","journal-title":"J. Org. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1021\/ja00768a037","article-title":"Hydrocyanation. IV. New hydrocyanation methods using hydrogen cyanide and an alkylaluminum, and an alkylaluminum cyanide","volume":"94","author":"Nagata","year":"1972","journal-title":"J. Am. Chem. Soc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.1021\/jo00122a042","article-title":"Stereoselective Construction of the Diterpene Part of Indole Alkaloids, Radarins, by Way of Intramolecular Diels-Alder Reaction","volume":"60","author":"Ihara","year":"1995","journal-title":"J. Org. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1021\/jo00356a030","article-title":"Bruceantin support studies. 10. Use of an axial alpha.-face control element in intramolecular conjugate additions: Synthesis of an ABCD tetracyclic bruceantin precursor","volume":"51","author":"Suryawanshi","year":"1986","journal-title":"J. Org. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/S0040-4020(01)88595-1","article-title":"Cyanotrimethylsilane as a versatile reagent for introducing cyanide functionality","volume":"39","author":"Utimoto","year":"1983","journal-title":"Tetrahedron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1021\/jo01290a005","article-title":"Synthesis of a model for the BCE ring system of bruceantin. A caveat on the cyclohexene fwdarw. trans diaxial diol conversion","volume":"45","author":"Dailey","year":"1980","journal-title":"J. Org. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8425","DOI":"10.1016\/S0040-4020(01)00825-0","article-title":"Common synthetic strategy for optically active cyclic terpenoids having a 1,1,5-trimethyl-trans-decalin nucleus: Syntheses of (+)-acuminolide, (\u2212)-spongianolide A, and (+)-scalarenedial","volume":"57","author":"Furuichi","year":"2001","journal-title":"Tetrahedron"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1055\/s-1995-4968","article-title":"Chemoselective Reduction of Carbonyl Compounds with Diisopinocampheylchloroborane","volume":"1995","author":"Cha","year":"1995","journal-title":"Synlett"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1021\/jo00036a026","article-title":"Total synthesis of tetronomycin","volume":"57","author":"Hori","year":"1992","journal-title":"J. Org. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1021\/jo971632f","article-title":"Advanced Tetracycles in a Stereoselective Approach to d,l-Spongiatriol and Related Metabolites:\u2009 The Use of Radicals in the Synthesis of Angular Electrophores","volume":"63","author":"Zoretic","year":"1998","journal-title":"J. Org. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1055\/s-1990-21218","article-title":"Monomeric Formaldehyde in Ethereal Solution","volume":"1990","author":"Schlosser","year":"1990","journal-title":"Synlett"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0040-4020(01)90005-5","article-title":"Total synthesis of dl-siccanin and dl-siccanochromene E","volume":"43","author":"Kato","year":"1987","journal-title":"Tetrahedron"},{"key":"ref_41","unstructured":"NOE spectroscopic date given in Supplementary Materials."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7400","DOI":"10.1021\/jo034838r","article-title":"Synthesis of (\u2212)-Nakamurol A and Assignment of Absolute Configuration of Diterpenoid (+)-Nakamurol, A","volume":"68","author":"Cuesta","year":"2003","journal-title":"J. Org. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1271\/bbb.65.1244","article-title":"Total Synthesis of (+)-Albicanol and (+)-Albicanyl Acetate","volume":"65","author":"Toshima","year":"2001","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10286","DOI":"10.1021\/ja1016975","article-title":"Total Synthesis of Enigmazole A from Cinachyrella enigmatica. Bidirectional Bond Constructions with an Ambident 2,4-Disubstituted Oxazole Synthon","volume":"132","author":"Skepper","year":"2010","journal-title":"J. Am. Chem. Soc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/4\/831\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:57:45Z","timestamp":1760173065000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/4\/831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,14]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["molecules25040831"],"URL":"https:\/\/doi.org\/10.3390\/molecules25040831","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,14]]}}}