NUCLEOSIDES AND NUCLEOTIDES .125. SYNTHESIS AND BIOLOGICAL EVALUATIONOF 2',3'-DIDEOXY-3'-FLUORO-2'-METHYLIDENE PYRIMIDINE NUCLEOSIDES

Reaction of 2'-deoxy-2'-methylidene-5'-O-trityluridine (1) with diethy lamino-sulfur trifluoride (DAST) in CH2Cl2 resulted in the formation o f a mixture of (3'R)-2',3'-dideoxy-3'-fluoro-2'-methylidene derivative 3 and 2',3'-didehydro-2',3'-dideoxy-2'-fluoromethyl derivative 4 (3:4 = 1:1.5) in 65% yield. A similar treatment of dene-5-O-trityl-beta-D- threo-pentofuranosyl)uracil (19) with DAST in CH2Cl2 afforded (3'S)-2' ,3'-dideoxy-3'-fluoro-2'-methylidene derivatives 20 and 4 in 38% and 1 7% yields respectively. Transformation of the uracil nucleosides 4, 12 , and 20 into cytosines followed by deprotection furnished the corresp onding cytidine derivatives 29, 18, and 25, respectively. The correspo nding thymidine congener 27 was also synthesized in a similar manner. All of the newly synthesized nucleosides were evaluated for their inhi bitory activities against HIV and for their antiproliferative activiti es against L1210 and KB cells.