title: Efficient chemoenzymatic synthesis of pelitrexol via enzymic differentiation of a remote stereocenter.
abstract: [structure: see text] An efficient chemoenzymatic process is described for the synthesis of pelitrexol, a novel GARFT inhibitor. The remoteness of this molecule's stereocenter in the tetrahydropterin moiety from the terminal carbonyl group provided a significant challenge in synthesis. The introduction of an oxalamic ester adjacent to the stereocenter dramatically enhanced an enzyme's enantioselectivity for hydrolysis at the terminal ester, producing the desired S-acid with high optical purity and yield. The recycling of the "wrong" enantiomer is achieved via a dehydrogenation/hydrogenation strategy.
authors.affiliation: Pfizer Global Research and Development, Chemical Research and Development, 10578 Science Center Drive, La Jolla, California 92121, USA. Shanghui.Hu@pfizer.com
authors.forename: Shanghui
authors.initials: S
authors.lastname: Hu
authors.forename: Sean
authors.initials: S
authors.lastname: Kelly
authors.forename: Steve
authors.initials: S
authors.lastname: Lee
authors.forename: Junhua
authors.initials: J
authors.lastname: Tao
authors.forename: Erik
authors.initials: E
authors.lastname: Flahive
mesh_terms: D002384:Catalysis; D005656:Fungal Proteins; D008049:Lipase / Q000378:metabolism; D015394:Molecular Structure; D051026:Phosphoribosylglycinamide Formyltransferase / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013876:Thiophenes / Q000138:chemical synthesis*
chemical_list: D005656:Fungal Proteins; D013876:Thiophenes; C516135:pelitrexol; D051026:Phosphoribosylglycinamide Formyltransferase; D008049:Lipase; C431349:lipase B, Candida antarctica