Design, Synthesis, and Study of Lactam and Ring-Expanded Analogues of Teixobactin.

ABSTRACT: This paper describes the chemical synthesis, X-ray crystallographic structure, and antibiotic activity assay of lactam analogues of teixobactin and explores ring-expanded analogues of teixobactin with β³-homo amino acids. Lactam analogues of teixobactin containing all four stereoisomers of aza-threonine at position 8 were synthesized on a solid support from commercially available stereoisomeric threonine derivatives. The threonine stereoisomers are converted to the diastereomeric aza-threonines by mesylation, azide displacement, and reduction during the synthesis. d-Aza-Thr₈,Arg₁₀-teixobactin exhibits 2-8-fold greater antibiotic activity than the corresponding macrolactone Arg₁₀-teixobactin. Azateixobactin analogues containing other stereoisomers

SUBMITTER: Yang H 

PROVIDER: S-EPMC7814697 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature