SYNTHESIS OF 6-DEOXY-6-PHENYLPHOSPHONOYL-D-FRUCTOPYRANOSES - THE 1ST PHOSPHORUS-IN-THE-RING ANALOGS OF A KETOSE

The title sugar analogues were synthesized through three routes, by st arting with three kinds of 6-O-tosyl-D-fructofuranoses. (i) Treatment of the known sopropylidene-1,6-di-O-tosyl-beta-D-fructofuranose succes sively with methyl iodide-silver oxide, sodium iodide and diethyl phen ylphosphonite provided ylidene-4-O-methyl-1-O-tosyl-beta-D-fructofuran ose in 67% overall yield. This was reduced with sodium dihydrobis(2-me thoxyethoxy)aluminate, followed by hydrolysis with acid, to afford a m ixture of the 4-O-methyl-1-O-tosyl and 1 -deoxy-4-O-methyl derivatives of the title compound. (ii) Treatment Of D-fructose with 2-methoxypro pene in the presence of TsOH and then with TsCl in pyridine afforded - O-isopropylidene-6-0-tosyl-alpha-D-fructofuranose (35% yield). This wa s subjected to the same five-step conversion, to give the 4-0-methyl d erivatives of the title compound. (iii) Treatment Of D-fructose with 2 ,2-dimethoxypropane-SnCl2 and then with TsCl-pyridine gave 2-0-isoprop ylidene-6-0-tosyl-beta-D-fructofuranose (23% yield). This was elaborat ed, in three steps, to either the -di-O-acetyl-6-deoxy-6-(ethoxy)phen ylphosphinoyl! derivative (84% yield) or the 3,4-bis-O-(tetrahydropyra n-2-yl) congener (54% yield), both of which furnished, in two steps, t he unsubstituted title compound. The products obtained in the three ap proaches (i-iii) were converted into the corresponding per-0-acetates, whose structures and conformations C-2(5)(D), C-5(2)(D), Or B3,6! we re established by spectroscopy.