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

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.