Practical synthesis, separation, and stereochemical assignment of the PMPA pro-drug GS-7340 |
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| Authors: | Chapman H Kernan M Prisbe E Rohloff J Sparacino M Terhorst T Yu R |
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| Affiliation: | Gilead Sciences, 333 Lakeside Drive, Foster City, California 94404, USA. |
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| 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 (S) by X-ray crystallography. |
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