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

Authors
Chapman, H Kernan, M Prisbe, E Rohloff, J Sparacino, M Terhorst, T Yu, R
Citation
H. Chapman et al., Practical synthesis, separation, and stereochemical assignment of the PMPApro-drug GS-7340, NUCLEOS NUC, 20(4-7), 2001, pp. 621-628
Citations number
11
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
ISSN journal
15257770 → ACNP
Volume
20
Issue
4-7
Year of publication
2001
Pages
621 - 628
Database
ISI
SICI code
1525-7770(2001)20:4-7<621:PSSASA>2.0.ZU;2-M
Abstract
The practical synthesis of a mixed phenoxy-amidate derivative of PMPA with high oral bioavailability and favorable pharmacokinetics is described. The nonstereoselective synthetic route produces a 1:1 mixture of two diastereom ers 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 (S) by X-ray crystallogr aphy.