Practical synthesis, separation, and stereochemical assignment of the PMPA pro-drug GS-7340

H Chapman, M Kernan, E Prisbe, J Rohloff…

Index: Chapman; Kernan; Prisbe; Rohloff; Sparacino; Terhorst; Yu Nucleosides, Nucleotides and Nucleic Acids, 2001 , vol. 20, # 4-7 p. 621 - 628

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Citation Number: 55

Abstract

The practical synthesis of a mixed phenoxy-amidate derivative of PMPA with high oral bioavailability and favorable pharmacokinetics is described. The non-stereoselective synthetic route produces a 1: 1 mixture of two diastereomers at phosphorous. Simulated moving bed chromatography using Chiralpak AS enabled kilo-scale isolation of the more potent diastereomer (GS-7340). The GS-7340 phosphorous chiral center was found to be ...