Modular Synthesis of the Potent Antibiotic Amycolamicin and Diastereomeric Analogues Thereof.

Yin X., Zhang Z., Yuan Z., Zhu Q., Xu P., Yang C-G., Zhu D., Yu B.

A modular approach to the potent, broad-spectrum antibiotic amycolamicin and seven diastereomeric analogues is described. The synthesis features bioinspired construction of the high-carbon amycolose segment, gold(I)-catalyzed high-yielding O-glycosylation of the trans-decalin scaffold, N-glycosylation of the bromoacetylated l-valine derivative, and condition-tuned late-stage C-acylation of the tetramic acid motif. An assessment of the antibacterial properties of these synthetic molecules indicated that the correct stereochemistry is essential for the potent bioactivity of amycolamicin.

DOI

10.1021/acs.orglett.5c00742

Type

Journal article

Publication Date

2025-04-11T00:00:00+00:00

Volume

27

Pages

3631 - 3636

Total pages

5

Keywords

Anti-Bacterial Agents, Catalysis, Glycosylation, Microbial Sensitivity Tests, Molecular Structure, Pyrrolidinones, Stereoisomerism, Glucosides, Pyrroles, Naphthalenes

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