DIASTEREOISOMERIC COMPOUNDS DERIVED FROM TETRAHYDROFOLIC ACID, PROCESS FOR THEIR PREPARATION AND USE IN THE SYNTHESIS OF DIASTEREOISOMERS 6S AND 6R OF REDUCED FOLATES

摘要

The present invention concerns a new process for preparing diastereoisomers derived from tetrahydrofolic acid. By the reaction of (i) (6RS)-folinic acid or one of its salts or (ii) 5,10-methenyl-5,6,7,8-tetrahydrofolic acid with HCOOH at a pH of 2.0-2.6, a precipitate is obtained consisting of a mixture of two diastereoisomers with an orthoamide structure and the formulae (III) and (IV) where R is the p-benzoyl-(L)-glutamic radical, in a molar ratio (IV/III) of about 7/3, with compound (III) of 'natural' configuration and compound (IV) of 'non-natural' configuration. Pure compound (IV) is isolated from said precipitate and pure compound (III) from the corresponding filtrate. From compound (III) and (IV) are prepared the diastereoisomers of the reduced folates and their natural and non-natural configuraton salts.