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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Total synthesis of Spiruchostatin A via chemoselective macrocyclization using an accessible enantiomerically pure
Nicole A Calandra1, Yim Ling Cheng, Kimberly A Kocak
1Department of Chemistry, Hobart College, Geneva, New York 14456, USA.
Abstract:
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.
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