{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:54:31Z","timestamp":1785894871650,"version":"3.56.0"},"reference-count":132,"publisher":"Wiley","issue":"52","license":[{"start":{"date-parts":[[2018,8,19]],"date-time":"2018-08-19T00:00:00Z","timestamp":1534636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000275","name":"Leverhulme Trust","doi-asserted-by":"publisher","award":["ECF-2015-013"],"award-info":[{"award-number":["ECF-2015-013"]}],"id":[{"id":"10.13039\/501100000275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/P029795\/1"],"award-info":[{"award-number":["EP\/P029795\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/N509802\/1"],"award-info":[{"award-number":["EP\/N509802\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2018,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Macrocyclic lactones can be prepared from lactams and hydroxyacid derivatives via an efficient 3\u2010 or 4\u2010atom iterative ring expansion protocol. The products can also be expanded using amino acid\u2010based linear fragments, meaning that macrocycles with precise sequences of hydroxy\u2010 and amino acids can be assembled in high yields by \u201cgrowing\u201d them from smaller rings, using a simple procedure in which high dilution is not required. The method should significantly expedite the practical synthesis of diverse nitrogen containing macrolide frameworks.<\/jats:p>","DOI":"10.1002\/chem.201803064","type":"journal-article","created":{"date-parts":[[2018,7,16]],"date-time":"2018-07-16T12:05:16Z","timestamp":1531742716000},"page":"13947-13953","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Iterative Assembly of Macrocyclic Lactones using Successive Ring Expansion Reactions"],"prefix":"10.1002","volume":"24","author":[{"given":"Thomas C.","family":"Stephens","sequence":"first","affiliation":[{"name":"University of York  York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aggie","family":"Lawer","sequence":"additional","affiliation":[{"name":"University of York  York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"French","sequence":"additional","affiliation":[{"name":"University of York  York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9169-5156","authenticated-orcid":false,"given":"William P.","family":"Unsworth","sequence":"additional","affiliation":[{"name":"University of York  York YO10 5DD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,19]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-018-0115"},{"key":"e_1_2_7_2_1","unstructured":"For prominent examples see:"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/348176a0"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2024119"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b03382"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.150.3693.178"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3863253"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.220.4600.949"},{"key":"e_1_2_7_9_1","unstructured":"\u00a0"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20000915)39:18<3315::AID-ANIE3315>3.0.CO;2-9"},{"key":"e_1_2_7_10_3","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3757(20000915)112:18<3453::AID-ANGE3453>3.0.CO;2-1"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00158a056"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol0607241"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00279a042"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja1082798"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1997-6121"},{"key":"e_1_2_7_16_1","unstructured":"\u00a0"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201609598"},{"key":"e_1_2_7_17_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201609598"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4SC03901G"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13711"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1039\/b926265b"},{"key":"e_1_2_7_21_2","first-page":"237","volume":"49","author":"Schmid F.","year":"2017","journal-title":"Synthesis"},{"key":"e_1_2_7_22_1","unstructured":"\u00a0"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol010263d"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1039\/C39860000413"},{"key":"e_1_2_7_25_1","unstructured":"\u00a0"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.6b00877"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo035145d"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3765(20021004)8:19<4346::AID-CHEM4346>3.0.CO;2-S"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja2108307"},{"key":"e_1_2_7_30_1","unstructured":"\u00a0"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b07403"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201601129"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200906355"},{"key":"e_1_2_7_33_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200906355"},{"key":"e_1_2_7_34_1","unstructured":"For other prominent iterative synthetic approaches see reference 1 and:"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11065"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b08958"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.201600264"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0716204"},{"key":"e_1_2_7_39_1","unstructured":"For reviews and perspective on the importance of macrocycles in medicinal chemistry see:"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2590"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm1012374"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm400887j"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4SC03089C"},{"key":"e_1_2_7_44_1","unstructured":"For selected prominent examples see:"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00907"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1580"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1584"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b10234"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm2007062"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01796"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-018-0006-y"},{"key":"e_1_2_7_52_1","unstructured":"\u00a0"},{"key":"e_1_2_7_53_2","first-page":"281","volume":"2","author":"Mcguire J. M.","year":"1952","journal-title":"Antibiot. Chemother."},{"key":"e_1_2_7_54_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.41.1029"},{"key":"e_1_2_7_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr960027u"},{"key":"e_1_2_7_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5386.63"},{"key":"e_1_2_7_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-009-2326-8"},{"key":"e_1_2_7_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17967"},{"key":"e_1_2_7_59_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b08577"},{"key":"e_1_2_7_60_1","unstructured":"\u00a0"},{"key":"e_1_2_7_61_2","doi-asserted-by":"publisher","DOI":"10.1086\/324626"},{"key":"e_1_2_7_62_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026033452159"},{"key":"e_1_2_7_62_3","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c2096"},{"key":"e_1_2_7_63_1","unstructured":"\u00a0"},{"key":"e_1_2_7_64_2","doi-asserted-by":"publisher","DOI":"10.1021\/j100343a077"},{"key":"e_1_2_7_65_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2md20176c"},{"key":"e_1_2_7_66_1","unstructured":"For macrocyclisation strategies in general see:"},{"key":"e_1_2_7_67_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1102629"},{"key":"e_1_2_7_68_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr0301402"},{"key":"e_1_2_7_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja910544p"},{"key":"e_1_2_7_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.1062"},{"key":"e_1_2_7_71_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201500068"},{"key":"e_1_2_7_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2683"},{"key":"e_1_2_7_73_2","unstructured":"Practical Medicinal Chemistry with Macrocycles E. Marsault M.\u2005L. Peterson Eds Wiley 2017."},{"key":"e_1_2_7_74_1","unstructured":"For reviews on classical methods for the synthesis of macrocyclic lactones including Yamaguchi macrolactonisation and ring closing metathesis methods see:"},{"key":"e_1_2_7_75_2","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-54348-1_9"},{"key":"e_1_2_7_76_2","first-page":"585","volume":"16","author":"Nicalaou K. C.","year":"1977","journal-title":"Tetrahedron"},{"key":"e_1_2_7_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4020(95)00629-M"},{"key":"e_1_2_7_78_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1cc10464k"},{"key":"e_1_2_7_79_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7NP00048K"},{"key":"e_1_2_7_80_1","unstructured":"For a recent review on ring expansion reactions see:"},{"key":"e_1_2_7_81_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201700467"},{"key":"e_1_2_7_82_2","unstructured":"M. Hesse Ring Enlargement in Organic Chemistry Wiley-VCH Weinheim 1991."},{"key":"e_1_2_7_83_1","unstructured":"For prominent examples of ring expansion methods for the synthesis of medium-sized and macrocyclic lactones see:"},{"key":"e_1_2_7_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)90653-7"},{"key":"e_1_2_7_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)90832-9"},{"key":"e_1_2_7_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)96972-8"},{"key":"e_1_2_7_87_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00464a047"},{"key":"e_1_2_7_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)87658-3"},{"key":"e_1_2_7_89_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.19840670708"},{"key":"e_1_2_7_90_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.19860690715"},{"key":"e_1_2_7_91_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.19870700207"},{"key":"e_1_2_7_92_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.19890720523"},{"key":"e_1_2_7_93_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00023a065"},{"key":"e_1_2_7_94_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00032a003"},{"key":"e_1_2_7_95_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00135a036"},{"key":"e_1_2_7_96_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo990041h"},{"key":"e_1_2_7_97_2","doi-asserted-by":"publisher","DOI":"10.1039\/b805797d"},{"key":"e_1_2_7_98_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201200425"},{"key":"e_1_2_7_98_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201200425"},{"key":"e_1_2_7_99_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.911"},{"key":"e_1_2_7_100_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1130"},{"key":"e_1_2_7_101_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.11.032"},{"key":"e_1_2_7_102_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2016.05.063"},{"key":"e_1_2_7_103_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13852"},{"key":"e_1_2_7_104_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201705645"},{"key":"e_1_2_7_105_1","unstructured":"\u00a0"},{"key":"e_1_2_7_106_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201509153"},{"key":"e_1_2_7_106_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201509153"},{"key":"e_1_2_7_107_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201605615"},{"key":"e_1_2_7_108_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201703316"},{"key":"e_1_2_7_109_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201703616"},{"key":"e_1_2_7_110_1","unstructured":"For a seminal study on ring closure reactions of medium sized rings and macrocycles see"},{"key":"e_1_2_7_111_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar00064a001"},{"key":"e_1_2_7_112_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201605714"},{"key":"e_1_2_7_112_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201605714"},{"key":"e_1_2_7_113_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201608198"},{"key":"e_1_2_7_113_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201608198"},{"key":"e_1_2_7_114_1","unstructured":"\u00a0"},{"key":"e_1_2_7_115_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)70936-1"},{"key":"e_1_2_7_116_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)99239-7"},{"key":"e_1_2_7_117_1","unstructured":"For an example of a similar reductiveN O-acetal forming reaction see reference 24b."},{"key":"e_1_2_7_118_1","unstructured":"Methods to prepare cyclicN O-acetals of this type are relatively rare but for previous methods see:"},{"key":"e_1_2_7_119_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol303073b"},{"key":"e_1_2_7_120_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol3030764"},{"key":"e_1_2_7_121_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo402768r"},{"key":"e_1_2_7_122_1","unstructured":"Full computational details can be found in the SI. To summarise the relative ground state energies of isomeric imide (8\/9) cyclol (10\/11) and ring expanded products (12\/13) were optimised using DFT\/B3LYP\/6-31G* (in a vacuum). Conformational searches of the optimised structures were performed at Molecular Mechanics Force Field (MMFF) level and all the generated structures were retained and their energies were calculated using DFT\/B3LYP\/6-31G*. The lowest energy geometry in each system was selected fully optimised and determined to be minima by the absence of negative vibrational modes using DFT\/B3LYP\/6-31G*. The final optimisation and frequency calculations were then done in a solvated model system (non-polar solvent) using DFT\/B3LYP\/6-31G*."},{"key":"e_1_2_7_123_1","unstructured":"Of additional note the same overall findings were observed (with very similar free energy difference) when the same systems were calculated using Hartree\u2013Fock calculations (HF\/6-31G*) with full details of included in the SI."},{"key":"e_1_2_7_124_1","unstructured":"For example expanded lactones (12\u2009f 13\u2009a 13\u2009fand17\u2009g) were prepared on 5\u2005mmol scale using the standard synthetic protocol with no appreciable reduction in yield."}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchem.201803064","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.201803064","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T17:36:35Z","timestamp":1760290595000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.201803064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,19]]},"references-count":132,"journal-issue":{"issue":"52","published-print":{"date-parts":[[2018,9,18]]}},"alternative-id":["10.1002\/chem.201803064"],"URL":"https:\/\/doi.org\/10.1002\/chem.201803064","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,19]]},"assertion":[{"value":"2018-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}