July 2022

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 Introduction2 Solid-Phase Synthesis of Daptomycin by an On-Resin Cyclization3 α-Azido Acids and Alternative Routes to Daptomycin by On-Resin Cyclization4 Synthesis of Daptomycin by an Off-Resin Cyclization5 SAR Studies on Daptomycin6 Oligomerization of Daptomycin on Membranes7 The Chiral Target of Daptomycin8 SAR Studies on Phosphatidylglycerol9 Conclusions

The C–H borylation strategy has spurred intense research endeavors due to the high atom- and step-economy it represents and because of the broad range of utilities of the resulting organoboranes. Nevertheless, this powerful transformation has had limited substrate scope and poor regioselectivity when it was applied to Lewis basic substrates (e.g., azines). The basic functionalities in substrates can coordinate to the metal centers, hindering the formation of products. Herein, we provide a brief overview of recent advances in transition-metal-­catalyzed regioselective C–H borylation of pyridines. Attention is paid to the latest contributions, which have demonstrated remarkable ­regioselectivity.1 Introduction2 para-Selective C−H Borylation3 meta-Selective C−H Borylation4 ortho-Selective C−H Borylation5 Summary