Synthetic studies on (+)-Citreoviral

Abstract

The tetrahydrofuran core of (+)-citreoviral was successfully synthesized via diastereoselective electrophile-promoted cyclization. Our synthetic approach employed the chiral alcohol (59) as starting building block by desymetrization of triol (60) which is accessible from commercially methallyl alcohol (61). Wittig reaction under salt-free conditions furnished the conjugated ester (57) which was transformed to allylic ester (94). Sharpless dihydroxylation of (94) gave the desired diol (95) in high yield. After protection and deprotection steps, terminal alkene was introduced to (95) efficiently, resulting in terminal alkene (107) which was converted to γ-hydroxyalkene (111). Iodocyclization of (111) furnished tetrahydrofuran derivative (113) in good yield as a single diastereomer which was confirmed by NOE experiment. This is known as an advanced intermediate to (+)-citreoviral. The key features in our synthetic approach are the desymmetrization of the 2-methylglycerol and the diastereoselective formation of the tetrahydrofuran.