Total Synthesis of Orbiculamide A

Orbiculamide A, a macrocyclic peptide with antimitotic and antileukemic properties, contains several synthetically challenging structural motifs, including a 2-bromo-5-hydroxytryptophan residue, that presents a widely recognized synthetic challenge. Here, we report the first total synthesis of orbiculamide A, where central to our approach is a chemoselective, late-stage bromodesilylation strategy. This work provides a foundation for the synthesis of related natural products and scaffold diversification of medicinal peptides.