Specific inhibitors in vitamin biosynthesis. Part 7. Syntheses of blocked 7,8-dihydropteridines viaα-amino ketones

Abstract

The synthesis of 15 blocked 7,8-dihydropteridines is described in which the pyrazine ring is built from a derivative of an α-amino ketone. Three routes to the amino ketones based upon amino acids, nitrosyl chloride addition to alkenes, and nitro alcohols are discussed. The compounds synthesised are inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, an enzyme in the pathway leading to dihydrofolate, and the inhibitory potencies of the compounds are discussed in the light of a hypothetical active site model for the enzyme.