Asymmetric Synthesis of Pochonin E and F, Revision of Their Proposed Structure, and Their Conversion to Potent Hsp90 Inhibitors

Citation:

Karthikeyan G, Zambaldo C, Barluenga S, Zoete V, Karplus M, Winssinger N. Asymmetric Synthesis of Pochonin E and F, Revision of Their Proposed Structure, and Their Conversion to Potent Hsp90 Inhibitors. Chemistry - A European Journal. 2012;18 (29) :8978-8986.

Abstract:

A concise and modular synthesis of pochonin E and F, and their epimers at C-​6 established the correct stereochem. of these two natural products to be (6R)​. Several members of the pochonin family have been shown to bind the heat shock protein 90 (Hsp90)​, which has been the focus of intense drug discovery efforts. Pochonin E and F as well as their epimers were derivatized into the corresponding pochoximes and further modified at the C-​6 position. Mol. dynamics simulations, docking studies, and Hsp90 affinity measurements were performed to evaluate the impact of these modifications.

Last updated on 11/21/2013