Pteridine-6-carboxamides

The dc polarography of a large group of pteridines in pH 2.0 phosphate buffer has been reported [85]. Three groups of pteridines (2,4,7-triamino-pteridines, 7-substituted-4-amino-2-aryl-5-pteridine carboxamides, and 4,7-diamino-2-aryl-5-pteridine carboximides) demonstrated polarographic reduction that was found to occur in two steps, to be pH-dependent, and to involve two electrons per step. 

Despite the fact that one of the first pteridine syntheses was based on an intramolecular Hofmann carboxamide degradation of pyrazine-2,3-dicarboxamide by action of potassium hypobromite and leads to lumazine (equation 104), (07CB4857), pyrazine derivatives in general have not often been used because of availability problems. The reaction of alkyl... 

Out of many hundreds of pteridines tested, 2,4,7-triamino-6-phenylpteridine (316), 4,7-diamino-2-phenylpteridine-6-carboxamide, 4-amino-7-(2-methoxyethylamino)-2-phenylpteridinecarbox-N-(2-methoxyethyl)amide (317) (69JPS(58)867) and 2,4-... 

Pteridine-7-carboxamide, JV-methyl-6-oxo-synthesis, 3, 310 Pteridine-4-carboxamides properties, 3, 276... 

In view of the importance in biochemical processes of pteridines such as folic acid, methotrexate, L-biopterin, and leucettidine <1996CHEC-II(7)679>, synthetic routes to fused pteridines continue to occupy considerable attention. Imidazo-fused pteridines have now been prepared from 3-aminopyrazine-2-carboxamides via carbodiimide intermediates. If the amido-nitrogen in the starting compound is further substituted, as in the scheme, the... 

Another key intermediate for pteridine synthesis was also seen in 2-amino-3-ethoxycarbonyl-5-phenylpyrazine 1-oxide which reacts with various amines to form the corresponding amides followed by cyclization with triethyl orthoformate giving 3-alkyl-6-phenyl-4(3/7)pteridinone 8-oxides <87JHC1109>. The synthesis of 2,4-diamino-6-methylpteridine 5-oxide (371) was achieved from 5-methyl-pyrazine-2-carboxamide (366) via the 4-oxide (367), a Hofmann degradation (368), bro-mination (369), and cyanation (370) followed by cyclization with guanidine to give (371) (Scheme 60) <93JHC841>. 

Pteridin-4-ones and pteridine-4-thiones are conveniently synthesized by this process. For example, 3-aminopyrazine-2-carboxamide can be converted into pteridin-4(3//)-one (1, X = O) by at least five different methods.18,37> 138 By refluxing it in a mixture of triethyl orthoformate and acetic anhydride a yield of 75% is obtained, whilst the use of 3-aminopyrazine-2-thio-carboxamide gives (1, X = S) in 84% yield.37... 

However, the use of carboxamidines and carboxamide oximes has been little explored. A related synthesis of interest is that of imidazo[l, 2-c]pteridine 6, and related compounds.142... 

Pyrazolo[3,4-b]pyrazines are useful intermediates for the preparation of 2-aminopyrazine-3-carboxamides such as 49, much used in pteridine syntheses. For example, reductive cleavage of the 1-substituted 3-hydroxy compound 48 with Raney nickel results in smooth breakdown of the pyrazole ring to give the product 49. 

The corresponding hydrochlorides do not react, so that the acetates seem to form a steady source of the more volatile and thermolabile bases. The course of the reaction is revealed by trichloroacetamidine, which takes the triazole no farther than an ethylideneamino derivative (153). This can be cyclized rapidly in cold 0.5 N potassium hydroxide to 2-trifluoromethyl-8-azapurin-6-one.248 Formamidine acetate has also been used to convert 2-aminopyrazine-3-carboxamide to pteridin-4-one in good yield.213... 

As indicated above, derivatives of folic acid play a key role in the biosynthesis of purines and pyrimidines. These pteridines are the coenzymes responsible for inserting the carbon atoms into both positions 2 and 8 of purines, and they also insert the methyl-group into thymine (4.7 ). When bacteria are treated with low concentrations of sulfonamides, 4-aminoimidazole-5-carboxamide ribotide 9.22) accumulates in the culture media. This substance is an intermediate in the biosynthesis of inosinic acid 9.23) from which all purines are derived. 

Albert A (1979) Pteridine studies. Part 46. 2-Alkylpteridin-4-ones from 2-aminopyrazine-3-carboxamide and its derivatives. J Chem Soc Perkin Trans 1 1574-1577... 

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