A Reverse Strategy for synthesis of nucleosides based on n-pentenyl orthoester donors.

Strategically derivatized NPOE glycosyl donors, are able to efficiently glycosylate silylated nucleobases under mild conditions, even as low as -78 °C if necessary. Ensuring trans-1,2 glycosylation, thus permitting, unlike classical procedures, a Reverse Strategy for the synthesis of ribonucleosides, where glycosylation occurs late, rather than early, and convergency is optimized.

Ready preparation of furanosyl n-pentenyl orthoesters from corresponding methyl furanosides.

The 3,5-di-O-benzoyl n-pentenyl orthoesters of the four pentofuranoses have been prepared. The first key intermediate in each case is the methyl pentofuranoside(s), and a user-friendly procedure for the preparation of each, based on the Callam-Lowary precedent, is described, whereby formation of the crucial α/β anomeric mixture is optimized. The mixture is used directly to prepare the corresponding perbenzoylated pentofuranosyl bromide(s) and then the title compounds.