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Updated: Aug 9, 2026
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Radiosynthesis of 1-(2-[18F]Fluoroethyl)-L-Tryptophan using a One-pot, Two-step Protocol
Published on: September 21, 2021
Efficient chemoenzymatic synthesis of pelitrexol via enzymic differentiation of a remote stereocenter
Shanghui Hu1, Sean Kelly, Steve Lee
1Pfizer Global Research and Development, Chemical Research and Development, 10578 Science Center Drive, La Jolla, California 92121, USA. Shanghui.Hu@pfizer.com
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.
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