616. Deoxynucleosides and related compounds. Part VII. The synthesis of 2′-deoxyuridine and of thymidine

Abstract

By D. M. BROWN, D. B. PARIHAR, C. B. REESE, and SIR ALEXANDER TODD. 5'-O-Acetyl-2'-O-toluene-fi-sulphonyluridine reacts with sodium iodide in hot acetonylacetone, to give 5'-O-acetyl-2'-deoxy-2'-iodouridine from which by hydrogenation and deacetylation 2'-deoxyuridine is obtained. The same route starting from 5'-O-acetyl-3-P-~-ribofuranosylthymine leads to thymidine. The synthetic deoxyribonucleosides are identical with the naturally occurring compounds.

Chemistry of the Nucleotides

“…Since the same iodo derivative was obtained by the action of sodium iodide and acetic acid on 5'-O-acetyl-02,2'-cyclouridine (to which it could be reconverted by treatment with base), Brown, Parihar & Todd (38) consider the cyclonucleoside to be an intermediate in the re placement of the toluene-p-sulphonyl group by iodination, the final product being the result of two displacements with inversion at 0'. The same proce dures applied to 5'-O-acetyl-3-,B-D-ribofuranosyl thymine yielded thymidine (37). In an alternate approach, Shaw & Warrener (39) treated 5' -O-trityl-5-methyl-2-thiouridine with methanesulphonyl chloride and obtained the cyclonucleoside directly.…”

“…Thus,S' -0-acetyl-2-0-toluene p-sulphonyl uridine on reaction with sodium iodide gave S'-O-acetyl-2' deoxy-2'-iodouridine, from which 2'-deoxyuridine was obtained by reduc tion and deacetylation (37). Since the same iodo derivative was obtained by the action of sodium iodide and acetic acid on 5'-O-acetyl-02,2'-cyclouridine (to which it could be reconverted by treatment with base), Brown, Parihar & Todd (38) consider the cyclonucleoside to be an intermediate in the re placement of the toluene-p-sulphonyl group by iodination, the final product being the result of two displacements with inversion at 0'.…”

Nucleosides LIII Syntheses and Reactions of 6,7-Dipyridyllumazine and 2' -Deoxylumazine N-1 Nucleosides

“…The inversion of the configuration at C-2' of the free nucleoside 7 was investigated by way of a 2,2'-an hydro deri vative 13 which has heen generated with the convenient diphenyl carbonate procedure (6,(19)(20)(21)(22). Thus, trea tment of 7 with diphenyl carbonate in DMF at 160°C showed a two step reaction : formation of the 2'.3'-0-carbonate derivative followed hy cyclization to the 2,2'-anhydro detivative 13 in 34% yield a fter loss of CO 2 • Compound 13 was further characterised as its diacetate 14.…”

The Synthesis of Nucleosides

“…However, in the first experiment in which the 2'-0-tosyluridine (XV, R=H) was allowed to react with sodium iodide in acetonylacetone at 1 0 0 "C, a high yield of a crystalline deoxyiodo derivative (XVI, R=H) was obtained, which after deacetylation and catalytic reduction gave 2'-deoxyuridine (XVII, R=H) [19]. In a similar manner, the corresponding derivr?tive of thymine (XV, R=CH3) was converted to thymidine (XVII, R=CH3) [20]. Normally one would expect the iodo derivative to have been formed by a single SN2 reaction, and consequently to have the arabo configuration, but elucidation of the reaction mechanism [8] showed that the iodide was a ribose compound (XVI).…”