Improved methods are described for accessing cyclic, cysteine-containing, depsipeptidic HDAC inhibitor natural products and their analogs via solid-phase synthesis.  The solid-phase tactics described here have been used to generate protected, linear, depsipeptidic precursors suitable for chemoselective macrocyclization.  The central development involves new organic reaction conditions for exploiting the latent thioester solid-phase linker that is crucial for the endgame macrocyclization.  The target depsipeptides belong to a class of HDAC inhibitors, and are thus intended as potential treatments for cancer and other ailments implicating HDAC.  Due to the variety of analogs available through this methodology, the synthetic targets will also be used to evaluate factors affecting HDAC inhibitory activity.

Depsipeptidic anticancer natural products and analogs via improved latent thioester mediated solid-phase methodology

243rd National Meeting (2012)

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