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.