SYNTHESIS OF 4'-FLUOROALKYL NUCLEOSIDE ANALOGS

The benzyl-protected 2,3-dideoxy-4-fluoroalkylriboses 14a-c have been obtained from beta-keto-gamma-fluoro-substituted sulphoxides 3a-c thro ugh: a) highly diastereofacial insertion of methylene from diazomethan e, b) transformation of the sulphinylmethyloxiranes 5a-c into the benz yloxymethyl derivatives 11a-c, c) epoxide ring opening with allylmagne sium chloride and oxidation of the introduced vinyl group to form the desired lactols 14a-c. Acetylation followed by catalyzed condensation with persilylated pyrimidine bases 16 and 24, reductive debenzylation and chromatographic separation afforded the final fluorinated nucleosi de analogues 19a-c. Accurate homo- and hetero-nuclear NOE experiments allowed assignment of the absolute stereochemistry at the anomeric pos ition.