A new method for producing antifolate agents having glutamic acid part in their structure or salt thereof with the general formula wherein M is a monovalent or divalent cation selected from group consisting of Na +, K +, 1/2Ca ++ or 1/2Mg ++; and R is with R 1 being a carbonyl group; and R 2 and R 3 being the same or different and being selected from - straight-chain or branched, saturated or unsaturated C 1 -C 20 -heteroalkyl groups, which can optionally be substituted with amino groups; - aromatic or aliphatic C 3 -C 18 -hydrocarbon rings, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups; - aromatic or aliphatic C 3 -C 18 -heterocycles, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups; or R 2 and R 3 either together form a phenyl or thiophene ring, which can be substituted with an alkyl group or alkyl group containing hetero atoms and alkyl groups can be further substituted with a bicyclic or heterocyclic ring systems containing structures like purines or pyrimidines; comprising reacting a compound of the following formula wherein R is the same as in formula, with an acid or base in a solvent; and the compounds of formula are obtained from reacting glutamic acid, N-substituted glutamic acids or their salts with chloroacetonitrile. M is a monovalent or divalent cation selected from group consisting of Na +, K +, 1/2Ca ++ or 1/2Mg ++; and R is with R 1 being a carbonyl group; and R 2 and R 3 being the same or different and being selected from - straight-chain or branched, saturated or unsaturated C 1 -C 20 -heteroalkyl groups, which can optionally be substituted with amino groups; - aromatic or aliphatic C 3 -C 18 -hydrocarbon rings, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups; - aromatic or aliphatic C 3 -C 18 -heterocycles, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups; or R 2 and R 3 either together form a phenyl or thiophene ring, which can be substituted with an alkyl group or alkyl group containing hetero atoms and alkyl groups can be further substituted with a bicyclic or heterocyclic ring systems containing structures like purines or pyrimidines; comprising reacting a compound of the following formula wherein R is the same as in formula, with an acid or base in a solvent; and the compounds of formula are obtained from reacting glutamic acid, N-substituted glutamic acids or their salts with chloroacetonitrile. R 1 being a carbonyl group; and R 2 and R 3 being the same or different and being selected from - straight-chain or branched, saturated or unsaturated C 1 -C 20 -heteroalkyl groups, which can optionally be substituted with amino groups; - aromatic or aliphatic C 3 -C 18 -hydrocarbon rings, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups; - aromatic or aliphatic C 3 -C 18 -heterocycles, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups; or - straight-chain or branched, saturated or unsaturated C 1 -C 20 -heteroalkyl groups, which can optionally be substituted with amino groups; - aromatic or aliphatic C 3 -C 18 -hydrocarbon rings, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups; - aromatic or aliphatic C 3 -C 18 -heterocycles, which can optionally be substituted with one or more selected from the group consisting of alkyl, alkenyl, alkynyl, carboxyl, hydroxyl, amine, nitro, thiol, sulfoxyl, sulfone groups; or R 2 and R 3 either together form a phenyl or thiophene ring, which can be substituted with an alkyl group or alkyl group containing hetero atoms and alkyl groups can be further substituted with a bicyclic or heterocyclic ring systems containing structures like purines or pyrimidines; comprising reacting a compound of the following formula wherein R is the same as in formula, with an acid or base in a solvent; and the compounds of formula are obtained from reacting glutamic acid, N-substituted glutamic acids or their salts with chloroacetonitrile.