PNAS 2010-11-30

Asymmetric phosphorylation through catalytic P(III) phosphoramidite transfer: enantioselective synthesis of D-myo-inositol-6-phosphate.

Peter A Jordan, Katherine J Kayser-Bricker, Scott J Miller

Index: Proc. Natl. Acad. Sci. U. S. A. 107(48) , 20620-4, (2010)

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Abstract

Despite the ubiquitous use of phosphoramidite chemistry in the synthesis of biophosphates, catalytic asymmetric phosphoramidite transfer remains largely unexplored for phosphate ester synthesis. We have discovered that a tetrazole-functionalized peptide, in the presence of 10-Å molecular sieves, functions as an enantioselective catalyst for phosphite transfer. This chemistry in turn has been used as the key step in a streamlined synthesis of myo-inositol-6-phosphate. Mechanistic insights implicate phosphate as a directing group for a highly selective kinetic resolution of a protected inositol monophosphate. This work represents a distinct and efficient method for the selective catalytic phosphorylation of natural products.