Enantiocontrolled synthesis of the epoxycyclohexenone moieties of scyphostatin, a potent and specific inhibitor of neutral sphingomyelinase

The epoxycyclohexenone moieties and of scyphostatin (), a potent and specific inhibitor of neutral sphingomyelinase, were synthesized in enantiomerically pure forms starting from (−)-quinic acid (). The synthetic method features (i) the preparation of the olefin masked enones and , the precursors for the key aldol-type coupling reaction, (ii) the efficient and stereocontrolled aldol-type coupling reactions between (or ) and benzaldehyde () and Garnerʹs aldehyde analogue to deliver alcohols and , respectively, both of which possess the requisite asymmetric quaternary carbon center at the C6 position, and (iii) the stereospecific SN2-type epoxide ring formation of the mesylates and under mild basic conditions to produce the targeted compounds and , respectively.