SYNTHETIC ELECTROCHEMICAL STUDIES ON NUCLEOSIDES .1. NOVEL METHOD FOR THE SYNTHESIS OF 2',3'-UNSATURATED NUCLEOSIDES VIA ELECTROLYSIS

A novel method for the synthesis of 2′, 3′-unsaturated nucleosides via electrochemical reductions of 2′(3′)-O-acyl-3′(2′)-deoxyhalonucleosides is described. Electrolysis of 9-(2, 5-di-O-acetyl-3-bromo-3-deoxy-β-D-xylofuranosyl)adenine (la) at −1.3 V vs. SCE in MeOH-AcONa (0.25 M) gave 9-(5-O-acetyl-2, 3-dideoxy-α-D-glycero-pent-2-enofuranosyl) adenine (2a) in 76% yield. The compound 2a was also obtained in 74% yield via electrolysis of a positional isomer 1b, 9-(3, 5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)adenine, under the same conditions. This electrochemical method could be extended to the synthesis of pyrimidine nucleosides (2b and 2c) using tetraethylammonium tosylate as an electrolyte in DMF solution. In the electrolysis of If in MeOH-AcONa (0.25 M), however, the extensive glycosidic cleavage followed by the formation of methyl 5-O-propionyl-2, 3-dideoxy-D-gZycero-pent-2-enofuranoside (6), furfuryl propionate (7), and uracil was observed, and 2c was obtained in only 38% yield. This glycosidic cleavage provides the first example of an electrochemical elimination of a halogen and an adjacent substituent bonded via a nitrogen atom. 3′-Deoxyadenosine (cordycepin) was obtained in 14% yield together with 3a (29%) and adenine (55%) via the electrolysis of 9-(3-deoxy-3-iodo-β-D-xylofuranosyl)adenine (Id) in MeOHAcONa (0.25 M). © 1979, American Chemical Society. All rights reserved.