2.4.5- Triamino-6-hydroxypyrimidine

The condensation of 2,4,5-triamino-6-hydroxypyrimidine and 5-deoxy-L-arabinose phenylhydrazone 1042, followed by oxidation of the intermediate 1043, gave biopterin 1044. The tetrahydrobiopterin is the natural cofactor of phenylalanine hydrolase. Various stereochemical isomers were also pre-... 

Recently it was discovered that cofactor activity with phenylalanine hydroxylase is not limited to tetrahydropterin derivatives. Thus, the substituted pyrimidines 2,4,5-triamino-6-hydroxypyrimidine (21) and 5-(benzylamino)-2,4-diamino-6-hydroxypyrimidine (22) are active in the L-phenylalanine hydroxylating system (78BBR(85)1614, 79JBC(254)5150, 80JBC(255)7774). The amine substituent at C-5 of (21) and (22) is apparently required for... 

One of the earliest syntheses of (11) involved condensation of a-bromo-/ ,/ -diethoxypropanal with 2,4,5-triamino-6-hydroxypyrimidine followed by oxidation of the resulting 5,6-dihydropterin (13) and hydrolysis of the acetal [37]. This early procedure is clearly equivocal, however, since the initial condensation reaction is known to lead to a mixture of regioisomers. The first... 

An early synthesis of folic acid developed by chemists at American Cyanamid involved condensation of 2,4,5-triamino-6-hydroxypyrimidine, 2,3-dibromopropionaldehyde and p-aminobenzoylglutamic acid (Scheme 3.9) [55a-d].This three-component procedure has become known as the Waller condensation, and has been widely employed for the synthesis of analogues because of the ease with which the various components of the condensation can be varied. Products from this three-component reaction, however, are mixtures of 6- and 7-substituted regioisomers. 

An early structural modification of FA and AP involved alkylation at C-9 and/or N-10. 10-MethylFA (447) [197] was prepared by reaction of 2,4,5-triamino-6-hydroxypyrimidine, 2,3-dibromopropionaldehyde and diethyl p-methylaminobenzoylglutamate (35), followed by alkaline hydrolysis (the Waller condensation). Analogous utilization of 2,2,3-trichlorobutyraldehyde and the requisite p-(JV-substituted amino)benzoylglutamate furnished (448a-c) (Scheme 3.88) [198]. The preparation of (450) by condensation of 2,4,5,6-tetraaminopyrimidine and the a-ketoacetal (449) was reported without details (Scheme 3.89) [199],... 

Source Green plant tissue, fresh fruit, liver, and yeast. Synthetic pteroylglutamic acid made by the reaction of 2,3-di-bromopropanol, 2,4,5-triamino-6-hydroxypyrimidine, andp-aminobenzoyl glutamic acid. 

The synthesis of folic acid was accomplished by the interaction of 2,4,5-triamino-6-hydroxypyrimidine and iV-( -aminobenzoyl)-L-glutamic acid in aqueous solution maintained at about pH 4 with ,j8-dibromopropionaldehyde... 

Reductone (HOCH=COH—CHO) has been condensed with ethyl N-(p-aminobenzoyl)glutamate to form ethyl iV-[/>-(2,3-dihydroxy-2-ene-propyl-idene-amino)-benzoyl]glutamate which can be condensed with 2,4,5-triami-no-6-hydroxypyrimidine to form folic acid . Another procedure for folic acid synthesis involves the alkylation of A -tosyl-/>-aminobenzoylglutamate with a substituted propylene oxide such as 2,3-oxidopropionaldehyde diethyl acetal, oxidation of the product to a ketone, condensation of the ketone derivative with 2,4,5-triamino-6-hydroxypyrimidine and finally removal of the tosyl group . Other three carbon unit reactants, such as condensed with />-aminobenzoyl glutamic acid to give useful intermediates for folic acid synthesis . 

However, 4,6-diamino-2-methylpyrimidine in alcoholic solution reacts with xylose to give 6-amino-4-D-xylosylamino-2-methylpyrimidine 48) The reaction of glucose and fructose with 2,4,5-triamino-6-hydroxypyrimidine yields pteridine compounds 50) which, when subjected to a folic acid -forming reaction, do not give biologically active compounds 50) ... 

An Amadori rearrangement was also found to take place as the first step in the reaction of o-glucose (1) with 2,4,5-triamino-6-hydroxypyrimidine (41) to give substituted pterine derivatives 42 (Scheme 11) [42]. Such compounds are important intermediates for the synthesis of folic acids and hydroxyalkylpterine and are of interest in context with the biogenesis of pterines 43 [43]. 

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