New Synthesis of l-Ribofuranose Derivatives from l-Xylose

Abstract

Since l-nucleosides and 2-deoxy l-nucleosides are finding more and more applications for the preparation of nucleases resistant “antisense” oligonucleotides¹ as well as for preparation of modified nucleosides as potential inhibitors of HIV,² efficient preparation of l-ribofuranose derivatives is needed. Although l-ribose was obtained by inversion of d-ribono-1,4-lactone followed by reduction,³ epimerization at C-2 of l-arabinose⁴ and inversion of configuration at C-2 of l-arabinose or at C-3 of l-xylose by displacement of a sulfonate group⁵ were also evaluated, but were found to be not very satisfactory. We recently published a preparation of l-ribofuranose derivatives from l-arabinose in which the configuration at C-2 was inverted by an oxidation-reduction sequence after suitable protection of O-3 and O-5.⁶ Although a high overall yield was obtained, upscaling was difficult because none of the intermediates were obtained in crystalline form. Therefore we decided to evaluate the same methodology starting from l-xylofuranose and we report herein our results.