Patent GB-733062-A (GB)
Title: Improvements in or relating to hydrogenated pteridine compounds and methods of producing same
IPC: C07D475/04
Filed: 1951-03-22
Abstract: The invention comprises 5,6-dihydro- and 5,6,7,8-tetrahydro-10-formyl pteridines having, in one tautomeric form, the general formul <FORM:0733062/IV (b)/1> and <FORM:0733062/IV (b)/2> wherein X represents a hydroxy or amino radical, Y represents a formyl radical and R represents a hydroxy radical or -COR represents an aliphatic amino acid amide radical, and their alkali metal and Group II metal salts, and processes for the preparation thereof by reducing with 1 or 2 molecular proportions of hydrogen a compound having, in one tautomeric form, the general formula <FORM:0733062/IV (b)/3> wherein X, Y and R have the above significance, or an alkali metal or a Group II metal salt thereof, and by treating a 5,6-dihydro- or a 5, 6, 7, 8-tetrahydro-pterin of the above general formula, wherein X and R have the above significance and Y represents hydrogen, or an alkali metal or Group II metal salt thereof with a formylating agent, e.g. in an inert solvent.  The reduction process may be carried out with or without the aid of a hydrogenation catalyst, e.g. platinum oxide, palladium on charcoal or Raney nickel catalyst.  The catalytic reduction may be effected in a solvent, e.g. water, formic acid, alcohol, glycol, acetic acid or dimethylformamide, and at a temperature from -20 DEG  to 150 DEG  C.  Reduction methods using metals or metal combinations are also suitable, e.g. sodium amalgam, zinc, aluminium amalgam, sodium borohydride, magnesium or magnesium amalgam, the reaction solvent being usually water or an essentially aqueous solvent in which alcohol or benzene is present.  Suitable formylating agents are formic acid and the esters and amides thereof and orthoformic acid, e.g. methyl, ethyl, butyl, benzyl and glycol formate, methyl and ethyl orthoformate, formamide, formamidine and formanilide. When alkyl formates are used it is preferable to carry out the reaction in the presence of an alkali metal alkoxide, pyridine, triethanolamine or any other tertiary amine.  In the examples, 5,6,7,8-tetrahydro - 10 - formylpteroylglutamic acid and the sodium salt thereof, 5,6-dihydro-10-formylpteroylglutamic acid and the sodium and magnesium salts thereof, and the sodium salt of 4-amino-5,6,7,8-tetrahydro-10-formylpteroylglutamic acid are prepared.  Similar hydrogenated pteridines in which the amide grouping is derived from glutamylglutamylglutamic and aspartic acid and serine are also referred to.  Formyl-pteridine compounds of the general formula <FORM:0733062/IV (b)/4> wherein X represents a hydroxy or amino radical, and R represents a hydroxy radical or -COR is an aliphatic amino acid amide radical, and the alkali metal and Group II metal salts thereof, are prepared by heating the corresponding free amine with formic acid and acetic anhydride. 5,6-Dihydro- and 5,6,7,8-tetrahydropteridines of the general formul <FORM:0733062/IV (b)/5> and <FORM:0733062/IV (b)/6> wherein X represents a hydroxy or amino radical, and R represents a hydroxy radical or -COR represents an aliphatic amino acid amide radical, are prepared by reducing the corresponding pteridines with 1 or 2 molecular proportions of hydrogen.  The following compounds are referred to :-5,6-di- and 5,6,7,8-tetra-hydropteroylglutamic acid and hydropteroylglutamylglutamylglutamic acid and 5,6-di- and 5,6,7,8-tetra-hydropteroic acid amides derived from aspartic acid, alanine and serine.