Tetsuo Tomishi

Nucleosides. Part 6. New chemical modification of the ribosyl moiety in uridines; synthesis of 2,2′-anhydro-1-[5-deoxy-5-(substituted thio)-β-D-arabinofuranosyl]uracil derivatives and their conversion into 3′,5′-epithiopyrimidine nucleosides

Treatment of 5-substituted 2′,5′-dichloro-2′,5′-dideoxyuridines (1) with thiols such as thiophenol, thioacetic S-acid, thiobenzoic S-acid, toluene-α-thiol, and ethanethiol in the presence of triethylamine or 1,1,3,3-tetramethylguanidine in N,N-dimethylformamide (DMF) gave the corresponding 2,2′-anhydro-1-[5-deoxy-5-(substituted thio)-β-D-arabinofuranosyl]uracils (2a–f) in good yield. Treatment of 5-substituted 2,2′-anhydro-1-(5-acetylthio-5-deoxy-β-D-arabinofuranosyl)uracils (2b) and (2f), prepared with ease by the reaction of (1) with thioacetic S-acid, with methanolic sodium methoxide gave the corresponding 1-(3,5-dideoxy-3,5-epithio-β-D-xylofuranosyl)uracils (9a) and (9c) fused with a thietane ring in the sugar moiety. None of the newly synthesized nucleosides displayed appreciable cytotoxicity or antiviral activity in primary rabbit cell cultures.

Nucleosides. Part 5. Isolation and characterization of the stable cyclic adducts, (5R,6S)- and (5S,6S)-bromo-O6,5′-cyclo-5,6-dihydrouridines in the bromination of 2′,3′-O-isopropylideneuridine with N-bromosuccinimide

Bromination of 2′,3′-O-isopropylideneuridine (1) with N-bromosuccinimide in chloroform containing acetic acid gave two diastereoisomeric cyclic adducts, (5R,6S)- and (5S,6S)-bromo-O6,5′-cyclo-5,6-dihydro-2′,3′-O-isopropylideneuridines (4a) and (4b), whose structures were determined on the basis of their chemical reactivities and 1H n.m.r. spectral results. The cyclic adducts (4a) and (4b) formed an equilibrium mixture under acidic conditions [(4a)/(4b)= 9:11], while under neutral and basic conditions both adducts were converted into 5-bromo-2′,3′-O-isopropylideneuridine (2).

Simple method for the synthesis of 5-substituted 2′,5′-anhydro-2′,5′-dideoxy-1-β-D-arabinofuranosyluracils

Reaction of 5-substituted 2′,5′-dichloro-2′,5′-dideoxyuridines (1) with methanolic sodium hydroxide under reflux afforded the corresponding 5-substituted 2′,5′-anhydro-2′,5′-dideoxy-1-β-D-arabinofuranosyluracils (2) in high yields.

SYNTHESIS OF 5-ARYLTHIOURIDINES VIA ELECTROPHILIC SUBSTITUTION OF 5-BROMOURIDINES WITH DIARYL DISULFIDES

Abstract Novel synthetic method of 5-arylthiouridine derivatives is described. Treatment of 5-bromo-2′,3′-O-isopropylideneuridine (1a) with diaryl disulfides in the presence of sodium hydride at ambient temperature gave the 5-arylthiouridines (2) in moderate yields. The present method is devised by virtue of a combination of efficient participation of the 5′-hydroxy group onto the uracil ring and the electrophilic nature of diaryl disulfide, which was applied to the synthesis of 5-arylthio-1-β-D-arabinofuranosyl-uracils (8).

New Chemical Modification of the Ribosyl Moiety in Uridines. : Synthesis of Novel Types of 3', 5'-Epithio Uridine Derivatives

Treatment of 5-substituted 5′-S-acetyl-2,2′-anhydro-5′-thio-1-β-D-arabinofuranosyluracils (2), prepared with ease from 5-substituted 2′,5′-dichloro-2′,5′-dideoxyuridines (1), with methanolic sodium methoxide gave the corresponding 3′,5′-epithio-3′,5′-dideoxy-1-β-D-xylofuranosyluracils (3) fused with a thietane ring in the sugar moiety.

Nucleosides. Part 3.1 Synthesis of 2-N-Substituted 1-β-D-Arabinofuranosylisocytosine Derivatives by The Reaction of 2′,5′-Dichloro-2′,5′-Dideoxyuridine with Amines

Abstract Reaction of 2′,5′-dichloro-2′,5′-dideoxyuridine (1) with ammonia and benzylamine afforded the corresponding 2-N-substituted 1-(5-chloro-5-deoxy-β-D-arabinofuranosyl)-isocytosine derivatives (2 and 10). Reaction of 1 with ammonia, methylamine, cyclohexylamine, and benzylamine followed by treatment with methanolic sodium methoxide gave the corresponding 2-N-substituted 1-(2,5-anhydro-β-D-arabino-furanosyl)isocytosine derivatives (6, 11, and 12).