Concise synthesis of (–)-cotylenol, a 14-3-3 PPI molecular glue

28 September 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Small molecules that modulate the 14-3-3 protein-protein interaction (PPI) network represent valuable therapeutics and tool com-pounds. However, access has been lost to 14-3-3 PPI molecular glues of the cotylenin class, leading to investigations into practi-cal chemical syntheses. Here we report a concise synthesis of (–)-cotylenol via a 10-step entry into the 5-8-5 cotylenin binding region using a convergent fragment coupling and Claisen-ene cascade.

Keywords

molecular glue
total synthesis
fusicoccane
leukemia

Supplementary materials

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Experimental procedures, characterization data and structural assignments.
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