Synthesis of Scyphostatin

Synthesis of Scyphostatin

Author: ChemistryViews

Scyphostatin is a potent reversible inhibitor of neutral sphingomyelinases (N-SMases), which are implicated in ceramide production and subsequent cell apoptosis (cell death). Its hydrophobic side chain moiety is thought to play a critical role in controlling both the reversibility and selectivity of N-SMase inhibition.

Thomas Pettus and co-workers, University of California, Santa Barbara, USA, have developed a strategy for the synthesis of scyphostatin analogues which permits late-stage manipulation of the hydrophobic chain while maintaining the epoxycyclohexenone motif.

A carboxylic acid cyclization component was used due to the incompatibility of sulfonamide-based cyclohexadienones with the epoxidation. The generation of enantiomerically pure cyclohexadienones was elucidated and could be employed in an epoxidation protocol without compromising the stereochemical integrity of the core.


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