SYNTHESIS OF A CENTRAL INTERMEDIATE IN THE BIOSYNTHESIS OF DIDEOXYSUGARS AND TRIDEOXYSUGARS

The synthesis of disodium (6-deoxy-alpha-D-ribo-hexopyran-3-ulosyl) (2 '-deoxythymidin-5'-yl) diphosphate (1) is described. To this end, D-gl ucose is transformed into known furanose derivative 2 possessing a 3-C -methylene group as latent functionality for 3-ulose generation. From 2, 3,6-dideoxy derivative 6 was synthesized; ensuing acid catalyzed cl eavage of the I,2-O-isopropylidene group and then O-acetylation furnis hed the required pyranose 8 alpha,beta, which could be selectively dea cetylated at the anomeric oxygen to afford 9 alpha,beta. Treatment wit h phosphitylating agent 13e and then oxidation led to dibenzylphosphat e derivative 15e which could be chemoselectively debenzylated by hydro genolysis without affecting the olefinic double bond (--> 17); de-O-ac etylation and then ozonolysis afforded the unprotected phosphate inter mediates 18 and 19, respectively. Both compounds could be successfully used for the synthesis of 1 by employing the nucleoside phosphate mor pholidate procedure for the generation of nucleoside diphosphate sugar s. Ozone cleavage of the olefinic double bond in 20 could be successfu lly performed even in the presence of the thymine moiety.