PURIFICATION OF PMPA AMIDATE PRODRUGS BY SMB CHROMATOGRAPHY AND X-RAY CRYSTALLOGRAPHY OF THE DIASTEREOMERICALLY PURE GS-7340

Abstract

The diastereomers of GS-7171, aryl phosphoramidate derivatives of the anti-HIV nucleotide analog 9-[2-R-(phosphonomethoxy)propyl]adenine (tenofovir, PMPA), were isolated by batch elution chromatography and continuous simulated moving bed chromatography. The absolute configuration of the more pharmacologically active diastereomer, GS-7340, was determined to be (R,S,S) by single crystal x-ray crystallography.

ACKNOWLEDGMENTS

The authors wish to thank Aerojet Fine Chemicals (Rancho Cordova, CA) for conducting the SMB chromatography, and the U.C. Berkeley X-Ray Crystallography facility for structure determination.