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.


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


  • A54145
  • Anti-Bacterial Agents
  • Lipoproteins