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. 2020 Mar 6;85(5):3812-3823.
doi: 10.1021/acs.joc.9b03443. Epub 2020 Feb 7.

Stereoselective Synthesis of Baulamycin A

Jonathan R Thielman  1 , David H Sherman  2 , Robert M Williams  1   3
Affiliations

Stereoselective Synthesis of Baulamycin A

Jonathan R Thielman et al. J Org Chem. .

Abstract

New structural classes of antibiotics are rare, structurally novel broad-spectrum antibiotics exceptionally so. The recently discovered baulamycins constitute a remarkable example of these highly prized compounds and, as such, have attracted considerable attention in the form of both synthetic efforts and biological studies. For the first time, we report a gram-scale preparation of the common carbon framework of the baulamycin family, as well as the total synthesis of its most potent member, baulamycin A. Our approach employs highly stereoselective, catalyst-controlled asymmetric conjugate additions to thioesters to set key stereocenters, as well as the first reported use of "dry ozonolysis" to reveal a masked carboxylic acid in the total synthesis of a natural product.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Structure of baulamycins A and B.
Scheme 1.
Scheme 1.. Retrosynthetic Analysis Based on Horner–Wadsworth–Emmons Coupling of LHS and RHS
Scheme 2.
Scheme 2.. Synthesis of Key RHS Intermediate 6
Scheme 3.
Scheme 3.. Synthesis of Key LHS Intermediate 5 and Coupling with LHS Aldehyde 6
Scheme 4.
Scheme 4.. Completion of the Synthesis of Baulamycin A
See this image and copyright information in PMC

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