Nucleoside Sultones: Synthons for the Preparation of Novel Nucleotide Analogues. 1. Synthesis and Ring-Opening Reactions

Article abstract of DOI:10.1021/jo00036a014

Treatment of either the 5'-O-tosyl or the 5'-O-mesyl derivative of 3'-O-mesylthymidine with lithium acetylide-ethylenediamine complex in DMSO affords the intramolecular 6,3-ester of 1,2,5,6-tetradeoxy-1-(3,4-dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)-β-D-erythro-hexofuranuronosulfonic acid (2).Similarly, the 5'-O-tosyl or 5'-O-mesyl derivative of 1-(2-deoxy-3-O-mesyl-β-D-threo-pentofuranosyl)thymine affords the intramolecular 6,3-ester of 1,2,5,6-tetradeoxy-1-(3,4-dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)-β-D-threo-hexofuranuronosulfonic acid (5).Sultone 5 reacts with a variety of nucleophiles to afford good yields of the corresponding 3'-substituted sulfonate salts (6, 7, 9, and 10) and, in some cases, the unsaturated nucleoside 8.Sultone 2 was generally much less susceptible to ring opening by nucleophiles.However, in the presence of base, nucleophilic substitution with azide ion did proceed via the intermediate anhydronucleoside, 11, to afford 6.Reaction of 2 with EtOH-NaOH afforded a 1:1 mixture of the epimeric 3'-hydroxy compounds 9 and 12.The above sulfonate salts represent interesting new isosteres of nucleoside 5'-O-phosphates.