Convergent Synthesis of Calcium-Dependent Antibiotic CDA3a and Analogues With Improved Antibacterial Activity via Late-Stage Serine Ligation

Org Lett. 2020 Jun 19;22(12):4749-4753. doi: 10.1021/acs.orglett.0c01544. Epub 2020 Jun 2.


A convergent synthesis via the late-stage serine ligation of naturally occurring calcium-dependent antibiotic CDA3a and its analogues has been developed, which allowed us to readily synthesize the analogues with the variation on the lipid tail. Some analogues were found to show 100-500-fold higher antimicrobial activity than the natural compound CDA3a against drug resistant bacteria. This study will enhance our understanding of CDA3a and provide valuable antibacterial lead candidates for further development.