Total synthesis of Spiruchostatin A via chemoselective macrocyclization using an accessible enantiomerically pure latent thioester.
HDAC inhibitor Spiruchostatin A was synthesized via a route that differs significantly from previously reported routes. The key step involves a latent thioester that initiates a chemoselective transformation similar to native chemical ligation to form the macrocyclic alanine-cysteine amide bond. The easily prepared latent thioester--the first such moiety reported in enantiomerically pure form--is designed with a pendant carboxylic acid to serve as a solid-phase linker for the synthesis of cyclic, cysteine-containing, peptidic materials.
Calandra
Nicole A
NA
Department of Chemistry, Hobart College, Geneva, New York 14456, USA.
Cheng
Yim Ling
YL
Kocak
Kimberly A
KA
Miller
Justin S
JS