Abstract
Daptomycin is a calcium-dependent cyclic lipodepsipeptide antibiotic that is used in the clinic for treating serious infections caused by Gram-positive bacteria. In this account, I present a summary of the research that has been conducted in my group on daptomycin’s total chemical synthesis, its structure–activity relationships, and its mechanism of action, since we began our studies a decade ago.
1 Introduction
2 Solid-Phase Synthesis of Daptomycin by an On-Resin Cyclization
3 α-Azido Acids and Alternative Routes to Daptomycin by On-Resin Cyclization
4 Synthesis of Daptomycin by an Off-Resin Cyclization
5 SAR Studies on Daptomycin
6 Oligomerization of Daptomycin on Membranes
7 The Chiral Target of Daptomycin
8 SAR Studies on Phosphatidylglycerol
9 Conclusions
Key words
antibiotics - daptomycin - solid-phase synthesis - mechanism - structure–activity relationships
