Syntheses of [5‐²H]‐uracil, [5‐²H]‐cytosine, [6‐²H]‐uracil and [6‐²H]‐cytosine

Abstract

SUMMARY 2Facile syntheses of [ 5-2H] -, [ 6-H] -uracil and [ 5-2H7-,[6-HI-cytosine were investigated. The catalytic reaction of uracil or cytosine with 2H2 gas in alkaline media gave rise to [6-HI-compounds almost exclusively. On the other hand, the reaction of 5-bromouracil or 5-bromocytosine with gave rise to a mixture of [5-H]-, 16-HI-and [5-2H,6-2H]-compounds depending on the experimental conditions. By controlling the temperature, the pressure of 2H2 gas and the amounts of catalyst, [5-HI-uracil and [5-HI-cytosine were obtained. The isotopic distribution in each product was measured by 'H NMR spectroscopy combined with an HPLC method.

Enzymatic De Novo Pyrimidine Nucleotide Synthesis

“…The major contributor is aspartate, and due to the wide availability of specifically labeled forms of aspartate, many specific pyrimidine base labeled patterns can be synthesized including a combination of 13 C, 15 N, and 2 H. The exchange of C 6 proton with solvent during the decarboxylation of OMP is convenient for specific deuteration schemes. Deuteration at the C 5 position is often desired since the H 5 and H 1 chemical shifts are very similar, and C 5 deuteration has been accomplished previously through a separate chemical synthesis of 2 H 5 - uracil . Using the de novo enzymatic synthesis scheme, selective deuteration on both the base and ribose with simultaneous 15 N labeling was successful in a single pot reaction.…”

“…Deuteration at the C 5 position is often desired since the H 5 and H 1 chemical shifts are very similar, and C 5 deuteration has been accomplished previously through a separate chemical synthesis of 2 H 5 -uracil. 31 Using the de noVo enzymatic synthesis scheme, selective deuteration on both the base and ribose with simultaneous 15 successful in a single pot reaction. There is one limitation placed on possible labeling patterns using this scheme due to the production of CO 2 by decarboxylation of OMP to UMP and 6-phosphogluconate to ribulose-5-phosphate during PRPP generation.…”

The Synthesis of Deuterionucleosides

“…C5, C6-2 H 2 uracil and cytosine can be synthesized using deuterium gas and a metal ion catalyst 79 . When uracil and cytosine are treated with 2 H 2 in alkaline media in the presence of a Pd catalyst, 6-2 H compounds are mostly formed (deuterium incorporation: 96 atom% for uracil, 79 atom% for cytosine), whereas 5-bromouracil and 5-bromocytosine produce mostly the 5-2 H derivatives.…”