Modular solid-phase synthesis of antiprotozoal barnesin derivatives.

Roman D, Raguž L, Keiff F, Meyer F, Barthels F, Schirmeister T, Kloss F, Beemelmanns C (2020) Modular solid-phase synthesis of antiprotozoal barnesin derivatives. Org Lett 22(10), 3744-3748. PubMed

Abstract

Here, we applied and optimized a solid support (SP)-based Horner-Wadsworth-Emmons reagent to prepare SP-bound vinylogous amino acids. Subsequent SP-based peptide synthesis, global deprotection, and chemical modifications yielded 14 lipodipeptides carrying vinylogous amino acids, including the natural product barnesin A (1). Biological evaluation revealed that several synthesized derivatives show micromolar to nanomolar inhibitory activity against papain-like cysteine proteases, human cathepsin L, and rhodesain.

Involved Units and Groups

Chemical Biology of Microbe-Host Interactions Transfer Group Anti-infectives

HKI-Authors

Dr. Christine Beemelmanns Dr. Florian Kloß Dr. Florian Meyer Luka Raguž Francois Keiff David Roman

Topics

Secondary metabolites from marine microbes

Identifier

doi: 10.1021/acs.orglett.0c00723 PMID: 32212714