Synthesis of unsaturated fluoride containing d- and l-pyranosyl nucleosides

Abstract

A series of fluorinated pyranosyl nucleosides in d- and l-configurations, 16, 19– 20, 25, 28– 29, have been synthesized. Starting from 1,2- O-isopropylidene- d-glyceraldehyde, homologated templates (3 S)- 6 and (3 R)- 6 were prepared by vinylation of fluoroenal 3, which were transformed to give allylic alcohols, 8 and 21, in three steps, respectively. The key intermediate triols 9 and 22 were obtained by O-benzoyl group migration from the primary hydroxyl group to the neighboring secondary hydroxyl group. Under basic conditions, ring closure reaction of 9 and 22 afforded unsaturated pyranosyl derivatives 10 and 23, respectively, while under acidic conditions unsaturated furanosyl compounds 12 were formed. N-Glycosylation of the pyranosyl acetates with silylated bases under Vorbrüggen conditions then gave the protected nucleosides, which were converted to the free nucleosides. However, condensation of the unsaturated furanosyl intermediate 12 did not provide the desired nucleosides. Structural and stereochemical assignments of the synthesized compounds were based on the NOESY spectra of 16a and 16b, as well as the X-ray crystal structure of 19a.