GB709574A - Improvements in or relating to tetrahydro compounds having the n formyl pteroyl-amino acid nucleus - Google Patents

Abstract

The invention comprises substituted N10-formyl - 5,6,7,8 - tetrahydro - pteridines of the general formula: <FORM:0709574/IV (b)/1> wherein X represents a hydroxyl or amino radical, R represents a hydroxyl radical or an N-glutamic or aspartic acid radical, and R1 and R2 represent hydrogen or chlorine, and a process for the preparation of the above compounds by reacting substantially 2 mols. of hydrogen with an N10-formyl-pteridine of the general formula: <FORM:0709574/IV (b)/2> wherein X, R, R1 and R2 have the above significance. The hydrogenation may be carried out in an inert solvent in the presence of a reduction catalyst, e.g. platinum oxide, palladium on charcoal or Raney nickel. Suitable inert solvents mentioned are water, formic acid, alcohols, glycol, acetic acid and dimethyl formamide. When reduction methods are employed using metals or metal combinations such as sodium amalgam, zinc, aluminium amalgam, sodium borohydride, magnesium amalgam or magnesium, the solvent is usually water or an aqueous solvent. The reduction temperature may be between 0 DEG and 150 DEG C. The N10-formylpteridine starting material for the above process may be prepared in situ by reacting the required 2-amino-4-substituted-9-methylpteroyl compound with a formylating agent to introduce the N10-formyl radical, and the product is then hydrogenated. The desired compounds may also be prepared by reacting a formylating agent with the required 5,6,7,8-tetrahydropteroyl compound. In the examples, the following compounds are prepared by formylating the corresponding pteridine with formic acid to introduce the N10-formyl radical, and treating the resulting N10-formylpteridine with hydrogen in the presence of platinum oxide: 5,6,7,8-tetrahydro-9-methyl-10 - formyl -, 5,6,7,8 - tetrahydro - 4 - amino - 9-methyl - 10 - formyl -, 5,6,7,8 - tetrahydro-31,51 - dichloro - 9 - methyl - 10 - formyl -, and 5,6,7,8 - tetrahydro - 4 - amino - 31 - chloro - 9-methyl - 10 - formylpteroylglutamic acid, 5,6,7,8 - tetrahydro - 21 - chloro - 9 - methyl-10-formylpteroic acid and the corresponding 4-amino-substituted compound, and 5,6,7,8-tetrahydro - 4 - amino - 9 - methyl - 10 - formylpteroylaspartic acid, and each compound is converted into its barium salt by reaction with barium chloride in neutral solution.