Regioselective deprotection of orthobenzoates for the synthesis of inositol phosphates

Abstract

Synthetic myo-inositol 1,4,5-triphosphate, Ins(1,4,5)P₃, and myo-inositol 1,3,4,5-tetraphosphate, Ins(1,3,4,5)P₄, continue to be valuable in biological studies. Inositol orthoesters have proved an important class of intermediate to access these compounds. We investigated the ability of steric bulk from a 4-O protecting group to direct DIBAL-H reduction of inositol orthobenzoates to generate the natural Ins(1,4,5)P₃ precursor 2,3,6-O-tribenzyl myo-inositol. Introduction of an equatorial 4-C-methyl group imparts totally selective reduction and we report the synthesis of novel 4-C-methyl-Ins(1,4,5)P₃ and 4-C-methyl-Ins(1,3,4,5)P₄.