Document Report Card

ID: ALA1275367

Journal: J Med Chem

Title: Diastereoselective synthesis of aryloxy phosphoramidate prodrugs of 3'-deoxy-2',3'-didehydrothymidine monophosphate.

Authors: Roman CA, Balzarini J, Meier C.

Abstract: The first diastereoselective synthesis of aryloxy phosphoramidate prodrugs of 3'-deoxy-2',3'-didehydrothymidine monophosphate (d4TMP) is reported. In our approach, (S)-4-isopropylthiazolidine-2-thione 1 was used as a chiral auxiliary to introduce the stereochemistry at the phosphorus atom. In the last step of the developed reaction sequence, the nucleoside analogue d4T was introduced to a stereochemically pure phosphordiamidate which led to the formation of the almost diastereomerically pure phosphoramidate prodrugs 8a-d (≥95% de). As expected, the individually prepared diastereomers of the phosphoramidate prodrugs showed significant differences in the antiviral activity. Moreover, the difference was strongly dependent on the aryl substituent attached to the phosphoramidate moiety.

CiteXplore: 20945915

DOI: 10.1021/jm100817f