Dihydropterin

There is no easy understanding of the spectral properties of these compounds in general, which may or may not have a built-in chromophoric system responsible for a long-wavelength absorption like 7,8-dihydropteridin-4-one or a blue-shifted excitation like its 5,6-dihydro isomer. More important than the simple dihydropteridine model substances are the dihydropterins and dihydrolumazines, which are naturally occurring pteridine derivatives and reactive intermediates in redox reactions. 

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). 

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... 

This interesting conversion of a five- into a six-membered heterocyclic ring was proven by the isolation of the enzyme GTP-cyclohydrolase from E. coli (71MI21600) and a similar one from Lactobacillus platarum (B-71MI21601) which catalyzes the reaction (300)(303). Dephosphorylation leads to 7,8-dihydro-D-neopterin (304), which is then cleaved in the side-chain to 6-hydroxymethyl-7,8-dihydropterin (305), the direct precursor of 7,8-dihy-dropteroic acid and 7,8-dihydrofolic acid (224). The alcohol (305) requires ATP and Mg " for the condensation with p-aminobenzoic and p-aminobenzoylglutamic acid, indicating pyrophosphate formation to (306) prior to the substitution step. 

Kuse, M., et al. (2001). 7,8-Dihydropterin-6-carboxylic acid as light emitter of luminous millipede, Luminodesmus sequoiae. Bioorg. Med. Chem. Lett. 11 1037-1040. 

Mouillon, J.M. et al., Folate synthesis in higher-plant mithocondria coupling between the dihydropterin pyrophosphokinase and the dihydropteroate synthase activities, Biochem. J., 363, 313, 2002. 

Molecular orbital calculations have been used to analyze the stabilities of dihydropterins <06H1705>. The photochemistry of 6-(hydromethyl)pterin in aqueous solution has been investigated <06HCA1090>. 

In this study, identification of the critical atomic and molecular determinants pertaining to the mechanism of dihydrofolate to tetrahydrofolate reduction was achieved by (i) ab initio quantum mechanics, (ii) molecular mechanics, and (iii) free energy perturbation techniques. For the first time, the complete free energy profile was calculated for the proton transfer from Asp27 of the enzyme E. Coli DHFR to the N5 position of the dihydropterin moiety of the substrate dihydrofolate. In addition, the free... 

This enzyme [EC 2.7.6.3], also known as 6-hydroxy-methyl-7,8-dihydropterin pyrophosphokinase and 7,8-dihydro - 6 - hydroxymethylpterin pyrophosphokinase, catalyzes the reaction of ATP with 2-ammo-4-hydroxy-... 

Drosopterin (87a) and isodrosopterin (87b) have been prepared by treatment of 7,8-dihydropterin (593) with p-hydroxy-a-ketobutyric acid (595) or a-hy-droxyacetoacetic acid (601) (506). Their initially proposed structures (507) have been revised to 87 (see Scheme 76) on the basis of detailed, H-NMR spectral analysis of 6,7-dimethyldrosopterin (602), which was prepared by treatment of 7-methyl-7,8-dihydropterin (603) with a-hydroxyacetoacetic acid (601) (50S). Structures of other drosopterins (88-90) have not yet been established. 

The importance of the dihydro and tetrahydro oxidation states of pterins in biology has stimulated interest in the study of the chemical properties of these compounds, especially with respect to electron-transfer and radical reactions. It has become apparent, perhaps unsurprisingly, that the stability and reactivity of these oxidation states are very sensitive to substituent effects and the much greater stability of the fully conjugated pteridines is most evident. The oxidation of tetrahydropterins and the reduction of dihydropterins have become especially important in the chemistry of nitric oxide production in nature and in oxidative stress but the accumulation of relevant facts has not led so far to a detailed understanding of the chemical property relationships. Relevant information is summarized in the following section. 

BH4 is essential for the AAHs to carry out their respective catalytic reactions and, at least for PAH, the prereductive activation, which appears to produce dihydrobiopterin quinonoid (g-BH2) directly (20). After the PAH catalytic cycle an oxygen atom is incorporated into the cofactor, providing 4a-OH-BH4 which dissociates from the active site. In order to regenerate the functional tetrahydro form of BH4 pterin carbinolamine dehydratase catalyzes the dehydration of 4-OH-BH4 to g-BH2, which is reduced back to by dihydropteridine reductase (Scheme 2). g-BH2 can also be converted to 7,8-dihydropterin (BH2) which can be regenerated to BH4 by dihydrofolate reductase (DHFR). 

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