Total Synthesis of Reported Structure of Baulamycin A and Its Congeners

Abstract

A convergent and flexible strategy for the stereoselective total synthesis of the reported structure of baulamycin A and its congeners has been developed for the first time. Synthetic highlights include a Crimmins aldol reaction to construct the C-1' and C-14 centers, a Crimmins acetate aldol reaction to generate the hydroxy group at the C-13 position, Horner-Wadsworth-Emmons olefination to form the C-C bond, and Evans methylation to install the C-8 center. This synthetic study disclosed that the reported structure of baulamycin A needs to be revised, as its spectroscopic data are not identical with those of the synthetic baulamycin A.

Synergy of synthesis, computation and NMR reveals correct baulamycin structures

“…During the course of our work, Guchhait et al reported a 17-step synthesis of the proposed structure of baulamycin A. 10 They similarly found that the data did not match and further attempts to prepare the correct diastereomer based on re-examination of the J-based configurational analysis was also unsuccessful.…”

Marine natural products

“…121 A total synthesis of the proposed structure of baulamycin A along with two diastereomers has been described in the literature. 126,127 Spectroscopic data discrepancies between the synthetic material and the NP indicate that the reported structure for baulamycin A needs to be revised. It is proposed that the actual structure of the MNP is most likely a different diastereomer.…”

Use of chiral auxiliaries in the asymmetric synthesis of biologically active compounds: A review

“…This substance, isolated from a marine microbiological source collected in Costa Rica and Papua New Guinea, is one of the members of a family of compounds that exhibit high activity against nonribosomal peptide synthetase‐independent siderophore (NIS) synthetases. On the basis of this precedent, Guchhait et al reported a synthetic route to obtain baulamycin A and its congeners using as a key step an asymmetric Evans' aldol reaction (Scheme ). The aldol reaction between aldehyde 113 and acyloxazolidinone 114 in the presence of TiCl 4 , DIPEA, and NMP led to intermediate 115 as the sole isomer.…”