H. Hrebabecky et al., PREPARATION OF CHLORO AND SULFANYL DERIVATIVES OF -HYDROXYMETHYL-ALPHA-L-THREO-PENTOFURANOSYL)URACIL, Collection of Czechoslovak Chemical Communications, 62(7), 1997, pp. 1114-1127
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.