Synthesis and Dihydropteridine Reductase [EC 1.6.99.10] (Human) Activity of Reduced 2,7-Dimethylpteridin-4(3H)-one, 2-Methyl-2-desaminoneopterin [6-(1' S,2' R-1' ,2' ,3' -trihydroxypropyl)-2-methylpteridin-4(3H)one] and 2-Methyl-2-desaminobiopterin [6-(1' R,2' S-1',2'-dihydroxypropyl)- 2-methylpteridin-4(3 H)-one]

Abstract

The syntheses of the title compounds have been achieved starting from 4,5-diamino-2-methylpyrimidin-6( 1 H)one. Sufficient amounts of the quinonoid 7,8-dihydropteridin-4(6H)-ones (12-14) were formed upon oxidation of the corresponding 5,6,7 ,8-tetrahydro derivatives (15 -17) to show that they are substrates of dihydroptcridine reductase (human). The apparent Km and Kcal values of (12-14) were determined. These provided evidence that the tautomeric form of the natural cofactor 7,8-dihydro(6H)biopterin has the endocyclic C2- N3 double bond structure (29).