Lipophilic 5,6,7,8-tetrahydropterin substrates for phenylalanine hydroxylase (monkey brain), tryptophan hydroxylase (rat brain) and tyrosine hydroxylase (rat brain)

Article abstract of DOI:10.1016/0223-5234(87)90265-0

A high yielding unambiguous synthesis of (+/-)-6-alkyl-5,6,7,8-tetrahydropterin 5a-f hydrochlorides starting from ethyl α-isocyanoacetate 1 and the respective alkanoic anhydrides or alkanoyl chlorides in four steps is described.All the six pterins 5a-f that have been synthesised are substrates for mammalian phenylalanine, tryptophan and tyrosine hydroxylases and their activities have been compared with those of natural 6R-tetrahydrobiopterin under similar conditions.The data allowed the choice of 6-n-propyl-5,6,7,8-tetrahydropterin 5c for further studies as a candidate for tetrahydrobiopterin drug therapy.Keywords: (+/-)-6-alkyltetrahydropterinsydroxylase / tryptophan hydroxylase / tyrosine hydroxylase