Second-generation synthesis of protected phosphonothiodifluoromethylene analogues of nucleoside-3′-phosphates

Abstract

A practical, eight-step synthesis of the key intermediate 14 in 19% overall yield from α- d-xylose is described. The preparation can be carried out on multi-gram scale and involves the use of the organomagnesium reagent 2d . The capability of derivative 14 to be transformed into the title compounds is examplified by the preparation of 15 . Additionally, X-ray crystallography of intermediate 12 provided the first structural data on difluorophosphonothioates.