Total Synthesis and Stereochemical Assignment of Micrococcin P1

摘要

This paper describes the total synthesis of the thiopeptide antibiotic micrococcin P1 (MP1,1; Figure 1), thereby estab-lishing its constitution and its configuration. Compound 1 is the major component of "micrococcin P", a cytotoxic extract isolated from Bacillus pumilus that consists of a roughly 7:1 mixture of 1 and of the corresponding ketone, 2, which is termed micrococcin P2 (MP2). MP1 binds tightly to ribo-somes, thereby disrupting protein synthesis. The compound thus exerts a potent antibiotic activity toward microorganisms, including the malarial parasite Plasmodium falciparum.