Collect. Czech. Chem. Commun. 1997, 62, 957-970


Hubert Hřebabecký, Miloš Buděšínský, Milena Masojídková, Zdeněk Havlas and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic


1-(2,3-O-Cyclohexylidene-4-C-hydroxymethyl-α-L-lyxofuranosyl)uracil (1) was converted in seven steps into 1-(2-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracil (8) and further into 1-(2-deoxy-4-C-hydroxymethyl-3,5-O-isopropylidene-α-L-threo-pentofuranosyl)uracil (9). Successive benzoylation, removal of the isopropylidene group, reaction with acetaldehyde diethyl acetal, and debenzoylation afforded (R)- and (S)-1-(2-deoxy-3,5-O-ethylidene-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracil (10a and 10b, respectively). Reaction of 1-(2-deoxy-4-C-triphenylmethyloxymethyl-α-L-threo-pentofuranosyl)uracil (14) with dichloromethane under conditions of phase transfer, followed by detritylation, afforded 1-(2-deoxy-4-C-hydroxymethyl-3,5-O-methylidene-α-L-threo- pentofuranosyl)uracil (15). Compound 14 was obtained from the derivative 8 by partial silylation, tritylation and desilylation. The absolute configuration of the isomeric ethylidene derivatives 10a and 10b was determined by NMR spectroscopy and the population of the deoxypentofuranose ring conformers was derived from the vicinal coupling constants J(H,H). The obtained results were compared with energy calculations. Neither of the prepared nucleoside analogues was active in vitro against HIV-1 and HIV-2.

Keywords: 4-C-Hydroxymethyluridine; Alkylidene derivatives; Conformational analysis.