4a-Hydroxytetrahydrobiopterin

Stepwise pyrazine ring-formation using 5-nitropyrimidine was applied to the synthesis of 4a-hydroxytetrahydrobiopterin (95), which is an interesting intermediate in the metabolism of aromatic amino acids (see Sect. 5.2). As illustrated in Scheme 18, the 5-aminopyrimidine 97 prepared from chloroni-tropyrimidine 96 by nucleophilic substitution followed by catalytic hydrogenation was oxidized under acidic conditions to o-quinone derivative 98. 

BH4 is converted to 4a-hydroxytetrahydrobiopterin (95) with incorporating one atom of dioxygen in the C(4a) position of pterin by the hydroxylation reaction catalyzed by aromatic amino acid hydroxylases (Scheme 32). The formation of 95 was observed in the reaction catalyzed by all three hydroxylases using UV spectroscopy [151]. Dehydration of 95 was carried out by the action... 

Finally,the(6i )-6-(L-erythro-l,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydrox-ypterin undergoes dehydration either spontaneously or with the aid of the 4a-hydroxytetrahydrobiopterin dehydratase enzyme (EC 4.2.1.96) to yield dihydro-biopterin, which can be recycled by reduction back to tetrahydrobiopterin with NADPH acting as a cofactor for 6,7-dihydropteridine reductase (EC 1.5.1.34). 

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