To pteridine oxide

Another approach uses the reaction of 6-chloro-5-nitropyrimidines with a-phenyl-substituted amidines followed by base-catalyzed cyclization to pteridine 5-oxides, which can be reduced further by sodium dithionite to the heteroaromatic analogues (equation 97) (79JOC1700). Acylation of 6-amino-5-nitropyrimidines with cyanoacetyl chloride yields 6-(2-cyanoacetamino)-5-nitropyrimidines (276), which can be cyclized by base to 5-hydroxypteridine-6,7-diones (27S) or 6-cyano-7-oxo-7,8-dihydropteridine 5-oxides (277), precursors of pteridine-6,7-diones (278 equation 98) (75CC819). 

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). 

Brown et al.68 have developed a cellulose plate with a fluorescent indicator. Compounds are developed in 3.0% (w/v) NHfc.Cl and detected by fluorescence quenching. These authors also use 0.5% mercaptoethanol in their mobile phase, but this is only to prevent oxidation of the labile reduced pteridines, which are not adequately protected by substitution at the N5 position. Since neutral or alkaline solutions of leucovorin are relatively stable in air, this precaution may not be required for routine assay. 

In a similar way, ethyl 3-amino-6-hydroxyiminomethyl-2-pyrazinecarboxylate 4-oxide (314) gave ethyl 3-amino-6-(5-phenylisoxazol-3-yl)-2-pyrazinecar-boxylate 4-oxide (315) (as before but using PhC=CH 55%) 836 also many analogues for elaboration to pteridines.836... 

The nucleophilic substitution, amination, aldol-type condensation, oxidation, and hydrolysis of the l//-pyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxide system, structurally related to pteridine, were studied in detail <03HCA139>. Chlorinated pyrazines were directly oxidized to their corresponding iV-oxides using dimethyldioxirane in a completely regioselective fashion <03HEC221 >. 1,6-Dibenzoyl-5//, 10//-diimidazo[ 1,5-a 1, 5 -[Pg.374]

The oxidations of 2-amino-3-cyanopyrazine 1-oxides to the 1,4-dioxides are described in Section VIII.3A(4) and deoxygenations of some 2-amino-3-cyano-pyrazine 1-oxides and 1,4-dioxides with phosphorus trichloride or sodium dithionite in Section VIII.3C(4). Deoxygenation and chlorination of aminocyanopyrazine 1-oxides are reported in Section V.IG, and deoxygenation and acetoxylation or alkoxylation of 2-amino-3-cyano-5-methylpyrazine 1,4-dioxide in Section VIII.3C(5). Hydrolysis of cyanopyrazine Y-oxides to carbamoylpyrazine Af-oxides are given in Section 10A(3) and ring closure reactions of 2-amino-3-cyanopyrazine 1-oxides to pteridine 8-oxides in Section V11I.3C(3). 

The formation of pteridines by the completion of the 1,2-bond has been rarely effective, although two examples are the cyclization of 3-(guanidinomethyl)pyrazin-2-amine (3) to give 3,4-dihydropteridin-2-amine, which is subsequently aromatized by oxidation to pteridin-2-amine (4), and the cyclization of 3-(ethoxycarbonylamino)methylpyrazin-2-amine to give 3,4-dihydropteridin-2(1 //)-one, which is also subsequently aromatized by oxidation.140-160-161... 

A striking feature of Mo(iv)-oxidized pterin systems is that metal chelation is coupled to pteridine protonation. This protonation is evidence of a change in the electronic structure within the Mo-pterin unit, where electron density is increased in the pteridine system through delocalization via... 

The diversity of folate vitamers is attributed to different oxidation states of the pteridine ring, the number of glutamic acid residues, and the type of one-carbon unit attached at positions 5 and/or 10 relative to the nitrogen atom [5,6], as illustrated in Figure 6.2. 

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