Pteridines lumazines

The structures of many polyhydroxypteridines have been investigated by Pfleiderer and his associates. Although 2,4-dihydroxy-pteridine (lumazine) appears to exist mainly in the dioxo form 182,... 

AT-Oxidation is very sensitive to steric effects, since 1-substituted lumazines and pterins give only 5-oxides and the presence of bulky substituents at position 7 also directs oxidation to N-5. The pteridine 5-oxide (52) and 8-oxide (53) and the 5,8-dioxide (55) contain the AT-oxide groups as such, even when the possibility of AT-hydroxy tautomers exists, as in (53) i(54). 

Radical anions have recently been detected during electrochemical reductions of lumazines (80H(14)1603) and are also assumed to be reactive intermediates in the reductive acylation of 2,4-disubstituted pteridines to the corresponding 5,8-diacyl-5,8-dihydro derivatives. 

The action of sulfur nucleophiles like sodium bisulfite and thiophenols causes even pteridines that are unreactive towards water or alcohols to undergo covalent addition reactions. Thus, pteridin-7-one smoothly adds the named S-nucleophiles in a 1 1 ratio to C-6 (65JCS6930). Similarly, pteridin-4-one (73) yields adducts (74) in a 2 1 ratio at C-6 and C-7 exclusively (equation 14), as do 4-aminopteridine and lumazine with sodium bisulfite. Xanthopterin forms a 7,8-adduct and 7,8-dihydropterin can easily be converted to sodium 5,6,7,8-tetrahydropterin-6-sulfonate (66JCS(C)285), which leads to pterin-6-sulfonic acid on oxidation (59HCA1854). 

There is also the possibility of removing the 2-oxo group by ring cleavage and subsequent recyclization. Lumazine can be hydrolyzed by strong alkali to 2-aminopyrazine-3-carboxylic acid (153) which is converted first into the amide (154) and then cyclized by ethyl orthoformate into pteridine-4-one (155 equation 47) (51JCS474). 

As a result of the 7r-deficiency of the pteridine nucleus, alkyl pteridines are activated in the a-positions. The common reactions based on C—H acidity are found with a wide variety of compounds. Bromination of 6- and 7-methyl groups leads to mono- and di-substitution selective formation of the monobromomethyl derivatives has not yet been achieved satisfactorily. 6-Methylisoxanthopterin is claimed to give the 6-bromomethyl derivative with bromine in acetic and sulfuric acids at 100 °C for 2 min (50ZN(B)132) and with 1,7-dimethyl-lumazine a 90% yield of the 7-bromomethyl derivative (60CB2668) is obtained after 4h... 

Various 6- and 7-methyl- and 6,7-dimethyl-pteridines bearing either oxo or amino groups in the 2- and 4-positions can be oxidized to the corresponding carboxylic acids by alkaline potassium permanganate on heating. Various lumazine and pterin mono- and di-carboxylic acids have been prepared in this way (48JA3026, 78CB3790). 

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... 

The degradation of more complex substances can be regarded as another route to pteridine derivatives. Already in 1895 tolualloxazine was oxidized by alkaline permanganate to lumazine-6,7-dicarboxylic acid, and further heating led in a stepwise decarboxylation to lumazine (3) (1895CB1970). 

Lee, J. (1990). Lumazine protein and the bioluminescence of Photobacterium. In Curtius, H.-C., et al. (eds.), Chem. Biol. Pteridines, Proc. Int. Symp. Pteridines Folic Acid Deriv., 9th, 1989, pp. 445-456. de Gruyter, Berlin. 

New derivatives of 4-amino and 2,4-diaminopteridines have been synthesized and their capability to inhibit neuronal nitric oxide synthase evaluated <99JMC4108>. The synthesis of folic acid multiply labeled with stable isotopes, for bioavailability studies in human nutrition, has been reported <99JCS(P1)1311>, Synthesis and antiviral evaluation of several 6-(methylenecarbomethoxy)pteridine-4,7-diones have been described <99JHC435>. Synthesis and biochemical evaluation of bis(6,7-dimethyl-8-D-ribityllumazines) as potential bisubstrate analog inhibitors of riboflavin synthase have been reported <99JOC4635>. Synthesis and cyclization of novel lumazine-enediyne chimeras have been reported <99H13>. 

This problem may, however, be a special case because the oxidation of pteridine alkenes in the presence of sensitive substituents such as alkylthio was shown to be possible using ligand-assisted catalysis with osmium tetraoxide or DMDO (Scheme 10). In the case of pteridine 65, a clean series of transformations to afford the pterin 66 was possible <20030BC664, 2005PTR53004/04>. However, if oxidation was carried out under moist conditions, the corresponding 2-oxopteridine (lumazine) was always obtained as illustrated by the conversion of 67 into the epoxide 68. 

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