SYNTHESIS OF 2-DEOXY-4-OCTULOSE DERIVATIVES BY HIGHLY DIASTEREOSELECTIVE ALKYLATIONS OF PROTECTED HEXULOSES

Reformatsky reaction of ,3:4,5-di-O-isopropylidene-beta-D-arabino-hexo s-2- ulopyranose 1 with methyl bromoacetate proceeded with high diaste reoselectivity to give methyl ropylidene-beta-D-manno-oct-4-ulo-4,8-py ranosonate 2 and its -D-gluco isomer 3, in an similar or equal to 10:1 ratio. Configurations of the new stereogenic centres (C-3) in 2 and 3 were determined by reduction of their ester groups to the related 2-d eoxy-4,5:6,7-di-O-isopropylidene-beta-D-manno- 4 and -D-gluco-oct-4-ul o-4,8-pyranose 5, respectively. When alkylation at C-1 of 1 was carrie d out with 2-lithio tert-butyl acetate, the corresponding tert-butyl e ster of 2 (6) and 3 (7) were formed in an similar or equal to 5.4:1 ra tio. The stereochemistry of 6 and 7 was established by their respectiv e reductions to 4 and 5. On the other hand, reaction of 1 with methyl methoxycarbonylmethylenedimethylsulfurane gave only methyl eta-D-glyce ro-D-galacto-oct-4-ulo-4,8-pyranosonate 8, whose stereochemistry was d emonstrated by its transformation to 4. On the other hand, Reformatsky reaction of -O-isopropylidene-alpha-L-xylo-hexos-2-ulofuranose 10 wit h methyl bromoacetate proceeded with moderate diastereoselectivity to give methyl ropylidene-alpha-L-gulo-oct-4-ulo-4,7-furanosonate 11 and its -L-ido isomer 12, in an similar or equal to 3.5:1 ratio. Configura tion of the new stereogenic centre (C-3) in 11, and hence in 12, was d etermined by degradation to the known dimethyl D-methoxymalate (+)-13. (C) 1997 Elsevier Science Ltd.