Synthesis of Piperazic Acid-Containing Cyclodepsipeptide Core of Verucopeptin Yuanjun Sun, Wenhao Tang, Mei Wang, Huxin Ni, and Ya-Qiu Long* Chin. J. Chem. 2023, 41, XXX—XXX. DOI: 10.1002/cjoc.202300XXX
Herein we reported an innovative strategy which enables the selective deprotection of N2-Cbz from N1,N2-diCbz piperazic acid-containing peptides, avoiding the introduction and removal of two orthogonal protecting groups of N1 and N2. We employ this method to the efficient synthesis of piperazic acid-containing cyclodepsipeptide core of verucopeptin in total 13 steps with an overall yield of 21%. The key steps include late stage coupling of piperazic acid-containing peptide and 3-hydroxyleucine derivatives, and HATU-mediated macrolactamization of 19-membered macrocycle at N9 and C10.