A simple and effective method for preparation of the 6(R)- and 6(S)-diastereoisomers of 5-formyltetrahydrofolate (leucovorin)

Abstract

Acylation of 6(RS)-tetrahydrofolate with (–)-menthyl chloroformate afforded an N-5 derivative which was separable into its diastereoisomers by extraction with n-butanol; these derivatives were converted separately into the 6(R)- and 6(S)-diastereoisomers of 5-formyltetrahydrofolate by treatment with a mixture of formic acid and hydrogen bromide in acetic acid followed by hydrolysis.