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Total Synthesis of Mycinolide IV and Path-Scouting for Aldgamycin N.

ABSTRACT: Proof-of-concept is provided that a large estate of 16-membered macrolide antibiotics can be reached by a "unified" 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-extended aldehyde by catalyst-controlled branch-selective asymmetric hydroformylation. These transformations ultimately opened access to two structurally distinct series of macrolide targets. Notable late-stage maneuvers comprise a rare example of a ruthenium-catalyzed redox isomerization of an 1,3-enyne-5-ol into a 1,3-diene-5-one derivative, as well as the elaboration of a tertiary propargylic alcohol into an acyloin by trans-hydrostannation/Chan-Lam-type coupling. Moreover, this case study illustrates the underutilized possibility of forging complex macrolactone rings by transesterification under essentially neutral conditions.

SUBMITTER: Herle B

PROVIDER: S-EPMC8048839 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Total Synthesis of Mycinolide IV and Path-Scouting for Aldgamycin N.

Herlé Bart B Späth Georg G Schreyer Lucas L Fürstner Alois A

Angewandte Chemie (International ed. in English) 20210226 14

Proof-of-concept is provided that a large estate of 16-membered macrolide antibiotics can be reached by a "unified" 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-extended aldehyde by catalyst-controlled branch-selective asymmetric hydroformylation. These transformations ultimately opened access to two structurally dist ...[more]

PMID: 33448619

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