Rapid and efficient routes to phosphatidylinositol 3,4,5-trisphosphates via myo-inositol orthobenzoate

Abstract

Efficient routes to two phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] analogues with different acyl chains have been developed by using cheaply available myo-inositol as the starting material. The high yield of the orthobenzoate derivative, preferential formation of the required protected inositol diastereomer in its desymmetrization and ease of separation make the synthesis expedient, economical and high yielding. Due to the inherent problem of racemization of diacylglycerol (DAG), the synthesis of phosphatidylinositol phosphates [PIPns] with unambiguous stereochemical purity has always been difficult. Our methodology excludes the possibility of racemization in the DAG unit and thus provides access to PtdIns(3,4,5)P3 of high optical purity. Since the acyl functionalities are introduced last, the methodology reported is amenable to the synthesis of PtdIns(3,4,5)P3 with any acyl chain (or even a library of analogues).