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

被引：62

作者：

Chapman, H ^{[1
]}

Kernan, M ^{[1
]}

Prisbe, E ^{[1
]}

Rohloff, J ^{[1
]}

Sparacino, M ^{[1
]}

Terhorst, T ^{[1
]}

Yu, R ^{[1
]}

机构：

[1] Gilead Sci Inc, Foster City, CA 94404 USA

来源：

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2001年 / 20卷 / 4-7期

关键词：

D O I：

10.1081/NCN-100002338

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 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 (S) by X-ray crystallography.

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页码：621 / 628

页数：8

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