Catalytic reduction in the synthesis of tritiated (6R) and (6S) 5, 10-dideaza-5,6,7,8-tetrahydrofolate

Abstract

[3H] 5,10-dideaza-5,6,7,8-tetrahydrofolate, DDATHF, was obtained by a two step process. First, 2n[3H2O] was produced in the reaction flask containing m[1HAc] by the reduction of n[PtO2] with 3H2, so that a 1[3H+]:18[3H+ + 1H+] ratio of solvent protic species in theory resulted. Secondly, subsequently added diethyl-2-acetyl-5,10-dideaza-9,10-didehydrofolate was reduced in this tritium labeled solvent with the pre-reduced Adams catalyst and additional carrier free tritium gas which was introduced to a pressure of 722 torr. The resulting (6R) and (6S) [3H] diastereomers were individually isolated. Each had a specific activity of 11.2 Ci/mmol, and the locations of the incorporated tritium atoms were completely determined by 1H decoupled 320 MHz 3H NMR by comparison with the 300 and 500 MHz 1H NMR spectra of [1H] (6S) DDATHF, [1H] (6R) DDATHF, and [5-2H (50% 2H), 6-2H (100% 2H), 7-2H (50% 2H), 9-2H (50% 2H), 10-2H (50% 2H)] (6RS) DDATHF.