{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:52:27Z","timestamp":1789145547822,"version":"build-2803163510"},"reference-count":132,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004189","name":"Max-Planck-Gesellschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004189","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2021,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Proof\u2010of\u2010concept is provided that a large estate of 16\u2010membered macrolide antibiotics can be reached by a \u201cunified\u201d approach. The key building block was formed on scale by an asymmetric vinylogous Mukaiyama aldol reaction; its alkene terminus was then converted either into the corresponding methyl ketone by Wacker oxidation or into a chain\u2010extended aldehyde by catalyst\u2010controlled branch\u2010selective asymmetric hydroformylation. These transformations ultimately opened access to two structurally distinct series of macrolide targets. Notable late\u2010stage maneuvers comprise a rare example of a ruthenium\u2010catalyzed redox isomerization of an 1,3\u2010enyne\u20105\u2010ol into a 1,3\u2010diene\u20105\u2010one derivative, as well as the elaboration of a tertiary propargylic alcohol into an acyloin by\n                    <jats:italic>trans<\/jats:italic>\n                    \u2010hydrostannation\/Chan\u2010Lam\u2010type coupling. Moreover, this case study illustrates the underutilized possibility of forging complex macrolactone rings by transesterification under essentially neutral conditions.\n                  <\/jats:p>","DOI":"10.1002\/anie.202016475","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T18:36:41Z","timestamp":1610735801000},"page":"7893-7899","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Total Synthesis of Mycinolide\u2005IV and Path\u2010Scouting for Aldgamycin\u2005N"],"prefix":"10.1002","volume":"60","author":[{"given":"Bart","family":"Herl\u00e9","sequence":"first","affiliation":[{"name":"Max-Planck-Institut f\u00fcr Kohlenforschung  45470 M\u00fclheim\/Ruhr Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Sp\u00e4th","sequence":"additional","affiliation":[{"name":"Max-Planck-Institut f\u00fcr Kohlenforschung  45470 M\u00fclheim\/Ruhr Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Schreyer","sequence":"additional","affiliation":[{"name":"Max-Planck-Institut f\u00fcr Kohlenforschung  45470 M\u00fclheim\/Ruhr Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0098-3417","authenticated-orcid":false,"given":"Alois","family":"F\u00fcrstner","sequence":"additional","affiliation":[{"name":"Max-Planck-Institut f\u00fcr Kohlenforschung  45470 M\u00fclheim\/Ruhr Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1128\/9781555819316"},{"key":"e_1_2_6_2_1","volume-title":"Macrolide Antibiotics. 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Agents Chemother."},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)97899-8"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/cber.19751080311"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.39.1776"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2009.6"},{"key":"e_1_2_6_14_1","unstructured":"\u00a0"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.34.346"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.34.1075"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.33.364"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2013.05.094"},{"key":"e_1_2_6_19_1","unstructured":"\u00a0"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.1361"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.1368"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.55.893"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17967"},{"key":"e_1_2_6_24_1","unstructured":"Protomycinolide\u2005IV:"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)91187-6"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00277a028"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.198610281"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.19860981121"},{"key":"e_1_2_6_28_1","unstructured":"Mycinamicin\u2005IV and VII:"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1246\/cl.1987.113"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4039(88)85296-1"},{"key":"e_1_2_6_31_1","unstructured":"For the synthesis of various fragments see:"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlac.199019900103"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1992-21289"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.3987\/COM-91-S79"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1246\/cl.2005.698"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja5071202"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.201803591"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00653"},{"key":"e_1_2_6_39_1","unstructured":"For examples of total synthesis projects from this laboratory which were not targeting a single individual compound but were a priori more integral see:"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202011472"},{"key":"e_1_2_6_40_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202011472"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c01700"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202015243"},{"key":"e_1_2_6_42_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202015243"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201501491"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201005850"},{"key":"e_1_2_6_44_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201005850"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200802067"},{"key":"e_1_2_6_46_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/B978-0-08-052349-1.00198-0","volume-title":"Comprehensive Organic Synthesis, Vol.\u20057","author":"Tsuji J.","year":"1991"},{"key":"e_1_2_6_47_1","unstructured":"\u00a0"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200802296"},{"key":"e_1_2_6_48_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200802296"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201006139"},{"key":"e_1_2_6_49_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201006139"},{"key":"e_1_2_6_50_1","unstructured":"\u00a0"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201507151"},{"key":"e_1_2_6_51_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201507151"},{"key":"e_1_2_6_52_2","first-page":"29","volume":"47","author":"Wong G. 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Since aldehyde6formed by Swern oxidation was isomerically pure (GC) and was freshly used some isomerization must occur during the vinylogous Mukaiyama reaction itself to explain the observed dr of 89:11."},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1039\/b617926f"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1039\/P19880000085"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol061202o"},{"key":"e_1_2_6_74_1","unstructured":"\u00a0"},{"key":"e_1_2_6_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-328X(02)01158-0"},{"key":"e_1_2_6_76_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1cs15071e"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja809542r"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200502485"},{"key":"e_1_2_6_78_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200502485"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c07808"},{"key":"e_1_2_6_80_1","unstructured":"Diastereomeric impurities derived from the minor isomer of the substrate could also be removed at this stage."},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201801023"},{"key":"e_1_2_6_82_1","unstructured":"The major issue seems to be the exceptional sensitivity of substrate and product towards basic conditions (LiOH in aq. MeOH\/THF; Ba(OH)2\u22c58\u2009H2O in MeOH) leading to intra- and\/or intermolecular addition of thetert-OH group to the enoate as well as partial or total cleavage of the TBDPS-ether; even the use of Me3SnOH in 1 2-dichloroethane furnished a complex mixture. Demethylation by SN2 reaction with LiI (in pyridine lutidine or DMF) gave small but variable amounts of theseco-acid (\u226445\u2009%) together with several unidentified side products."},{"key":"e_1_2_6_83_1","unstructured":"\u00a0"},{"key":"e_1_2_6_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)84989-8"},{"key":"e_1_2_6_85_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00018a019"},{"key":"e_1_2_6_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202016477"},{"key":"e_1_2_6_86_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202016477"},{"key":"e_1_2_6_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)61244-3"},{"key":"e_1_2_6_88_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol034608z"},{"key":"e_1_2_6_89_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja055967n"},{"key":"e_1_2_6_90_1","unstructured":"For the formation of six-membered lactones see ref. 28 and the following:"},{"key":"e_1_2_6_91_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja067305j"},{"key":"e_1_2_6_92_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201002932"},{"key":"e_1_2_6_93_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201701391"},{"key":"e_1_2_6_93_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201701391"},{"key":"e_1_2_6_94_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201311080"},{"key":"e_1_2_6_94_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201311080"},{"key":"e_1_2_6_95_1","unstructured":"\u00a0"},{"key":"e_1_2_6_96_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b01475"},{"key":"e_1_2_6_97_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b12517"},{"key":"e_1_2_6_98_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201801344"},{"key":"e_1_2_6_99_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b09782"},{"key":"e_1_2_6_100_1","unstructured":"Similar problems of transannular interference are known for several other 16-membered macrolide antibiotics including erythromycin\u2005B; for representative cases see ref.\u2005[17b] and the following:"},{"key":"e_1_2_6_101_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo01282a051"},{"key":"e_1_2_6_102_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo201319b"},{"key":"e_1_2_6_103_1","unstructured":"The use of BOBPhos was critical; several other ligands were also screened but found inadequate."},{"key":"e_1_2_6_104_1","unstructured":"Even at slightly higher temperatures reversibleisomerization of the terminal alkene to various internal positions (\u201cchain walk\u201d) becomes a serious issue leading to the formation of regio- and stereoisomers (scrambling of the C6 stereocenter); at lower temperatures the reaction rates are unacceptably slow."},{"key":"e_1_2_6_105_1","unstructured":"As the aldehyde gets partly oxidized on storage it was used in the next step without delay."},{"key":"e_1_2_6_106_1","unstructured":"In the accompanying study [47]it was found that reactions at higher concentration resulted in low yields whereas further dilution did not lead to significant improvements. 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Electronic effects of the phosphine ligand however may also play a role see ref.\u2005[63] and the following: K. 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