posted on 2006-04-13, 00:00authored byShanghui Hu, Sean Kelly, Steve Lee, Junhua Tao, Erik Flahive
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.