Total Synthesis and Structural Establishment/Revision of Antibiotics A54145

Delin Chen; Hoi Yee Chow; Kathy Hiu Laam Po; Wenjie Ma; Emily Lok Yee Leung; Zhenquan Sun; Ming Liu; Sheng Chen; Xuechen Li

doi:10.1021/acs.orglett.9b01972

Total Synthesis and Structural Establishment/Revision of Antibiotics A54145

Org Lett. 2019 Jul 19;21(14):5639-5644. doi: 10.1021/acs.orglett.9b01972. Epub 2019 Jul 2.

Authors

Delin Chen¹, Hoi Yee Chow¹, Kathy Hiu Laam Po², Wenjie Ma¹, Emily Lok Yee Leung¹, Zhenquan Sun¹, Ming Liu¹, Sheng Chen², Xuechen Li¹

Affiliations

¹ Department of Chemistry, State Key Laboratory of Synthetic Chemistry , The University of Hong Kong , Hong Kong , P. R. China.
² Department of Applied Biology and Chemical Technology, State Key Lab of Chiroscience , The Hong Kong Polytechnic University , Hung Hom, Kowloon, Hong Kong , P. R. China.

PMID: 31265311
DOI: 10.1021/acs.orglett.9b01972

Abstract

A54145 is a family of antibacterial cyclic lipodepsipeptides structurally resembling daptomycin. Since its discovery in 1990, only the ambiguous structures of the methoxy-aspartic acid (MeO-Asp) and the hydroxy-asparagine (HO-Asn) have been reported. We have developed efficient routes to obtain the fully protected l-MeO-Asp and l-HO-Asn building blocks compatible with Fmoc-SPPS, and a total synthesis of A54145 that enabled us to establish its structure, consisting of l-3S-HO-Asn and l-3R-MeO-Asp, revising the wrongly proposed structure of l-3S-MeO-Asp.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry*
Chemistry Techniques, Synthetic
Lipoproteins / chemical synthesis
Lipoproteins / chemistry
Microbial Sensitivity Tests

Substances

A54145
Anti-Bacterial Agents
Lipoproteins