A total synthesis of (+)-pisiferol

Abstract

A total synthesis of (+)-pisiferol (1) has been accomplished by utilising an optically active Wieland–Miescher ketone analogue (S)-(+)-(6) bearing an angular protected hydroxymethyl group, as the key intermediate. Reductive methylation of the monoacetal (7) of compound (6), followed by Huang–Minlon reduction, gives the trans-decalone acetal (9). Construction of the remaining carbocycle leading to the dodecahydrophenanthrenone (14) is achieved through five sequential reactions (deprotection, methoxycarbonylation, Michael addition with methyl vinyl ketone, demethoxycarbonylation, and intramolecular aldol cyclisation). After introduction of the 2-hydroxypropan-2-yl side-chain, dehydration followed by base-catalysed aromatisation affords pisiferol methoxymethyl ether (18). Finally, hydrolysis furnishes (+)-pisiferol (1).