Total chemical synthesis of lassomycin and lassomycin-amide

Abstract

Herein we report a practical synthetic route to the lasso peptide lassomycin (1) and C-terminal variant lassomycin-amide (2). The biological evaluation of peptides 1 and 2 against Mycobacterium tuberculosis revealed that neither had any activity against this bacterium. This lack of biological activity has led us to propose that naturally occurring lassomycin may actually exhibit a standard lasso peptide threaded conformation rather than the previously reported unthreaded structure.