Asymmetric phosphorylation through catalytic P(III) phosphoramidite transfer: enantioselective synthesis of D-myo-inositol-6-phosphate.
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.
Jordan
Peter A
PA
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520-4900, USA.
Kayser-Bricker
Katherine J
KJ
Miller
Scott J
SJ
D055162:Biocatalysis; D007202:Indicators and Reagents; D007295:Inositol Phosphates / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D013237:Stereoisomerism
D007202:Indicators and Reagents; D007295:Inositol Phosphates; D009943:Organophosphorus Compounds; C434331:phosphoramidite