Synthesis of γ-[15N]-L-glutamyl derivatives of 5,10-dideazatetrahydrofolate

Abstract

A synthesis of the mono-, di-, and tri[15N]glutamate forms of the potent de novo purine synthesis inhibitor and anticancer agent (6R,6S)-5,10-dideaza-5,6,7,8-tetrahydrofolate (6R,6S-DDATHF) from (6R,6S)-5,10-dideaza-5,6,7,8-tetrahydropteroic acid is described. These isotopically labelled compounds are potentially useful as 15N nmr probes of the interaction of DDATHF and its polyglutamates with three key enzymes of one-carbon metabolism, glycinamide ribonucleotide formyltransferase, (GARFT), aminoimidazolecarboxamide formyltransferase (AICARFT), and folypolyglutamate synthetase (FPGS). Copyright © 1999 John Wiley & Sons, Ltd.