Pteridines, XCV

Abstract

A series of new amino acid-tetrahydropterin-conjugates has been synthesized starting from N 2-isobutyryl-6,7- dimethyl-5,6,7,8-tetrahydropterin (7). The amino acids have been attached in form of their esters (10 - 16) via a succinyl spacer to the N-5 position (17 - 23) or directly via the carboxyl function applying CBZprotected activated esters (35, 39). Acylation of 7 with N-benzyloxycarbonylglutamic acid anhydride led to the y-glutamyl derivative 41. Selective deblocking experiments were achieved by catalytic hydrogenolysis to cleave the benzyl esters (24-28, 36, 42) and by DBU treatment to eliminate the p-nitrophenylethyl group (24, 25) respectively. Further reaction with ammonia hydrolysed the isobutyryl group to give the free tetrahydropterin-amino acid-conjugates 29 - 32, 37 and 43. Also a carbamoyl-type conjugate (45) was obtained from 7 and benzyl phenylalanine N-carbonylimidazolide (44). The newly synthesized compounds have been characterized by elemental analysis, UV and IH-NMR spectra.