Abstract: (6S)-THF is obtained by adding, in portions, an acid to an aqueous solution of a (6RS)-diastereoisomeric mixture of an alkali metal salt of 5,6,7,8-tetrahydrofolic acid. The addition is made at a temperature from 5.degree. C. to 80.degree. C. for the purpose of the selective crystallization for a period sufficient to stabilize the pH to a value of from 4.8 to 5.3. Then, the formed solid, i.e., (6S)-5,6,7,8-tetrahydrofolic acid, is separated.

Abstract: A process for the preparation of salts of (6R)-N(5),N(10)-methenyl-5,6,7,8-tetrahydrofolic acid of a particular formula (I). The process comprises:(i) mixing at least one acid S.sub.1 with an aqueous solution having dissolved therein an ammonium- or alkali metal-salt of (6RS)-N(10)-formyl-5,6,7,8-tetrahydrofolic acid of a particular formula (II) until a pH in the range of about 5.5 to 7.5 is obtained;(ii) adding a water-soluble alkaline earth metal salt to the mixture obtained from step (i);(iii) precipitating a solid and isolating the solid;(iv) providing a solid of formula (I) by suspending the solid obtained from step (iii) in water, adding an acid S.sub.2, which will not precipitate with an alkaline earth metal cation, until the pH stabilizes to a value of 1.0 to 2.0, and separating the resulting solid.

Abstract: There are described ammonium salts of N.sup.5 -methyl-5,6,7,8-tetrahydrofolic acid as well as processes for their preparation. These ammonium salts may be separated into the single (6R) and (6S)-diastereoisomers. The separated diastereoisomers may be transformed into the corresponding alkali metal or alkaline earth metal salts.

Abstract: A process for the preparation of alkaline earth metal salts of (6R)-N(10)-formyl-5,6,7,8-tetrahydrofolic acid. An alkaline earth metal salt, either in the form of a solid, or in the form of an aqueous solution, is added, preferably under an inert gas atmosphere, to an ammonium salt or alkali metal salt of (6RS)-N(10)-formyl-5,6,7,8-tetrahydrofolic acid dissolved in water or an aqueous buffer solution. II is added an alkaline earth metal salt either in the form of a solid or in the form of an aqueous solution. The obtained mixture is allowed to crystallize, and the obtained solid is separated. The product is known to be cytostatic.

Abstract: The present invention relates to a novel method of preparing diastereoisomers derived from tetrahydrofolic acid. By reacting (i) (6RS)-folinic acid or one of its salts, or (ii) 5,10-methenyl-5,6,7,8-tetrahydrofolic acid, with HCOOH at pH 2.0-2.6, a precipitate is obtained which consists of a mixture of two diastereoisomers of orthoamide structure and of the formulae ##STR1## in which R is the p-benzoyl-(L)-glutamic acid residue, in a molar ratio IV/III of about 7/3, compound III being of so-called natural configuration and compound IV being of so-called unnatural configuration. The pure compound IV is isolated from said precipitate and the pure compound III is isolated from the corresponding filtrate. The diastereoisomers of the reduced folates and their salts of natural and unnatural configuration are prepared from compounds III and respectively IV.

Abstract: There are described ammonium salts of N.sup.5 -methyl-5,6,7,8-tetrahydrofolic acid as well as processes for their preparation. These ammonium salts may be separated into the single (6R) and (6S)-diastereoisomers. The separated diastereoisomers may be transformed into the corresponding alkali metal or alkaline earth metal salts.