PREPARATION OF CHLORO AND SULFANYL DERIVATIVES OF -HYDROXYMETHYL-ALPHA-L-THREO-PENTOFURANOSYL)URACIL

3'-Chloro and 3'-acetylsulfanyl derivatives of -hydroxymethyl-alpha-L- threo-pentofuranosyl)uracil were prepared by reaction of 2,3'-anhydro- 1-[5'-O-benzoyl-4'-C-[(benzoyloxy yl]-2'-deoxy-alpha-L-erythro-pentofu ranosyl}uracil (3) with hydrogen chloride and thioacetic acid, respect ively. The reaction with hydrogen chloride gave a mixture of N-1 and N -3 substituted uracil derivatives 12 and 14. Reaction of ethyl]-2-deox y-alpha-L-threo-pentofuranosyl}uracil (7) with thionyl chloride and su bsequent debenzoylation afforded ethyl-2-deoxy-beta-D-erythro-pentofur anosyl)uracil (19). Nucleophilic substitution with lithium thioacetate , followed by deacylation, converted luenesulfonyl]-alpha-L-threo-pent ofuranosyl}uracil (9) into ulfanylmethyl-beta-D-erythro-pentofuranosyl )uracil (21). The obtained thiols were oxidized with iodine or air to give ofuranose-3,1-diyl]di(pyrimidine-2,4-/1H,3H-dione) (17) and ofura nose-5,1-diyl]di(pyrimidine-2,4(1H,3H)-dione) (22). Reaction of ]-2,3- dideoxy-alpha-L-threo-pentofuranosyl)}uracil (24) with methanolic sodi um methoxide afforded nyl-3-sulfanyl-alpha-L-threo-pentofuranosyl)urac il (25). The same reagent was used in the preparation of 1-(3,5-anhydr o-2- -hydroxymethyl-alpha-L-threo-pentofuranosyl)uracil (26) from olue nesulfonyl-alpha-L-threo-pentofuranosyl}uracil (8). From the series of 4'-substituted 2'-deoxyuridine derivatives, synthesized in this study , solely the 4'-chloromethyl derivative 19 and the oxetane derivative 26 exhibited an appreciable activity against HIV-1 and HIV-2.