Pteridine derivatives

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. 

A great variety of differently substituted pteridine derivatives have been synthesized starting from (109) or the 2,4,6,7-tetrabromo compound (60USP2940972), which shows a corresponding reactivity pattern. Amines at low temperature substitute only the 6- and... 

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). 

Oettl, K. and Reibnegger, G., Pteridine derivatives as modulators of oxidative stress, Curr. Drug Metab., 3, 203, 2002. 

Pteridine derivatives. The allylaminopteridinone 251, when treated with iodine, undergoes cyclization similar to that already described in Section 12.17.3.1 (Scheme 37) to give the imidazopteridinone 252 (Equation 78) <1996J(P1)247>. 

A mixture of Gly, c-Ala, L-Val, c-Lys, c-Asp, and l-G1u was heated without a solvent at 160-200°C, thereby simulating prebiotic conditions. Several tricyclic heterocycles and a pteridine derivative were isolated from the reaction mixture (79AG510). 

Dopamine is the decarboxylation product of DOPA, dihydroxyphenylalanine, and is formed in a reaction catalysed by DOPA decarboxylase. This enzyme is sometimes referred to as aromatic amino acid decarboxylase, since it is relatively non-specific in its action and can catalyse decarboxylation of other aromatic amino acids, e.g. tryptophan and histidine. DOPA is itself derived by aromatic hydroxylation of tyrosine, using tetrahydrobiopterin (a pteridine derivative see Section 11.9.2) as cofactor. 

Folate, the anion of folic acid, is made up of three different components—a pteridine derivative, 4-aminobenzoate, and one or more glutamate residues. After reduction to tetrahydrofolate (THF), folate serves as a coenzyme in the Q metabolism (see p. 418). Folate deficiency is relatively common, and leads to disturbances in nucleotide biosynthesis and thus cell proliferation. As the precursors for blood cells divide particularly rapidly, disturbances of the blood picture can occur, with increased amounts of abnormal precursors for megalocytes megaloblastic anemia). Later, general damage ensues as phospholipid... 

Tautomerism is common in pteridine derivatives and the favored tautomers should be represented by the structural formulas. Amino groups exist as such and not in the iminodihydro form whereas the hydroxy and thiol functions 9 located adjacent or para to a ring nitrogen atom prefer the thermodynamically more stable amide (lactam) and thioamide (thioxo) configuration 8 (Scheme 1) . 

In some cases, side reactions were observed. When 4-chlorophenyl isocyanate reacted with iminophosphorane 135 (R= Pr ), along with the corresponding pteridin-4(377)-one (43%), the hydrolyzed compound, 3-isopropylpteridine-2,4-(177,377)-dione (26%), was also isolated. In cases with additional functional groups in the pteridine substrate such as esters, polycyclic compounds such as the imidazo[2,T ]pteridine derivative 138 (37%) were obtained. Similarly, Wallyl and W(l-methylprop-2-enyl) groups in 137 gave imidazo[2,l- ]pteridines 139 by iodoamination. 

The one-step synthesis of further tri- and tetracyclic pteridine derivatives from 2-aminopyrazine 153 has also been described <2001JHC1173>. Cyclic analogues of A -[bis(methylthio)methylene]amino reagents such as 2-(methylthio)-2-thiazoline, 5,6-dihydro-2-(methylthio)-4//-l,3-thiazine, 2-(methylthio)-2-imidazoline, 2-(methylthio)-l,4,5,6-tetrahydro-pyrimidine, 2-(methylthio)-2-pyrazine, and 2-chloropyrimidine reacted with aminopyrazine 153 to afford thiazolo/thia-zino[2,3-3]- 159 ( = 1 (53%), n = 2 (42%)), imidazo/pyrimidino[2,l-/ ]- 160 ( = 1 (53%), = 2 (57%)), pyrazino[2,l-/ ]-161 (21%), and pyrimido[2,l-/ ]-pteridine 162 (42%) derivatives, respectively. 

Pyrazine 168 underwent cross-coupling with propyne in the tri-o-tolylphosphine, and copper(l) iodide to provide 170. The isocyanate or methyl chloroformate and sodium hydride to give An isolated example of the synthesis of chiral pteridines from a (Scheme 33). 2-Isothiocyanatopyrazine-3-carboxylates have been isothiocyanatopyrazine-2-carboxylate 172 reacted with R)- —) provided the pteridine derivative 173 and uncyclized pyrazine with pyridine precursors afforded pyrido[2,3 Pytitnidines. 

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