Lumazine,

The structure of lumazine has been studied more precisely by X-ray analysis (72AX(B)659). The crystal structure is built up of almost coplanar, hydrogen-bonded dimers of lumazine with the oxygens of the pyrimidine moiety in the keto form and the observed bond distances indicating the pyrazine ring electrons to be delocalized. 

Table 5 Physical Data for 8-Substituted Lumazines and Pterins...

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). 

Direct sulfurizations of simple monooxopteridines have not been successful, but the more stable lumazines and 2-thiolumazines are good substrates for P4S10 treatment, leading... 

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). 

The a-ionization of 7-methylpteridines can also be utilized in aldol-type condensation reactions. 7-Methyl-pterin and -lumazine and 2,4-diaminopteridine condense readily in aqueous base with aromatic aldehydes to afford 7-alkylidenepteridines (77JOC2951). A Claisen condensation requires the protection of the acidic hydrogens of the amide bonds. 

Little information is available about 5,6-dihydropteridines, of which various 6,7-diphenyl-5,6-dihydropterins (65HCA764, 69HCA306) and -lumazines (68HCA1029, 70HCA789) have been synthesized and characterized. As noticed already (51BSF521), this type of compound isomer-izes in an acid-catalyzed reaction to the 7,8-dihydro derivative (77HCA922) or oxidizes to... 

An unusual approach to the lumazine nucleus was found in the photochemical transformation of 6-azido-l,3-dimethyluracil (289) with various amino compounds (78JA7661). Irradiation of (289) in the presence of ethyl a-amino acid esters forms 7-substituted 7,8-dihydrolumazin-6-ones (288), and with a-aminoketones 6-substituted 7,8-dihydro-lumazines (290) are formed (equation 103). 

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). 

All compounds of this heterocyclic ring system so far found in nature are derivatives of pterin (2) and lumazine (3) carrying different substituents in the 6- and/or 7-positions. The most common representatives of these series are listed in Tables 8 and 9. 

Lumazinecarboxylic acid Violapterin Lumazine-6-carboxylic acid —... 

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