Abstract: The present invention relates to stable crystalline (6S)—N(5)-formyl-5,6,7,8-tetrahydrofolic acid, commonly referred to as levofolinic acid, in essentially pure 6S diastereomeric form, and to a process for its preparation.

Abstract: The present invention relates to stable crystalline (6S)—N(5)-formyl-5,6,7,8-tetrahydrofolic acid, commonly referred to as levofolinic acid, in essentially pure 6S diastereomeric form, and to a process for its preparation.

Abstract: New process for the production of (6S)-5,6,7,8-tetrahydrofolic acid or derivatives thereof starting from the corresponding (6S, 6R) racemic mixture. The procedure comprises in the steps of adding an organic acid to a non-alkaline suspension of (6S,6R)-5,6,7,8-tetraydrofolic acid, up to a pH value in the range of 1 to 3; heating the suspension from 30° to 80° C.; cooling the suspension from 20° to 60° C., with selective crystallization of the (6S)-isomer. The procedure gives the (6S)-isomer in high yields and with a high degree of stereoselectivity. It follows that the synthetic access to a large number of pharmacologically active stereoisomers of folic acid is simpler and more-effective.

Abstract: New process for the production of (6S)-5,6,7,8-tetrahydrofolic acid or derivatives thereof starting from the corresponding (6S, 6R) racemic mixture. The procedure comprises in the steps of adding an organic acid to a non-alkaline suspension of (6S,6R)-5,6,7,8-tetraydrofolic acid, up to a pH value in the range of 1 to 3; heating the suspension from 30° to 80° C.; cooling the suspension from 20° to 6O° C., with selective crystallization of the (6S)-isomer. The procedure gives the (6S)-isomer in high yields and with a high degree of stereoselectivity. It follows that the synthetic access to a large number of pharmacologically active stereoisomers of folic acid is simpler and more-effective.

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.