The thio-Mitsunobu reaction: a useful tool for the preparation of 2,5-anhydro-2-thio- and 3,5-anhydro-3-thiopentofuranosides.
The unprotected methyl L-arabinofuranosides, D-ribofuranosides and D-xylofuranosides are transformed into the corresponding S-acetyl-5-thio derivatives by the thio-Mitsunobu reaction. Mesylation and subsequent reaction with sodium hydrogen carbonate led, depending on the configuration of the intermediate, to 2,5-anhydro-2-thio- or 3,5-anhydro-3-thiopentofuranosides. Due to inversion at C-3 or C-2 during the intramolecular nucleophilic displacement the products exhibit L-lyxo-, D-arabino- or D-lyxo-configuration. Analogously, the methyl 2,3-anhydro-D-ribofuranosides yielded 5-thio-S-acetates with intact 2,3-oxirane groups, which were cyclised with sodium hydrogen carbonate by epoxide ring opening and concomitant ring closure to form exclusively 3,5-anhydro-3-thio-D-xylofuranosides. A related 3,5-anhydro-3-seleno-D-lyxofuranoside was obtained by reaction of a 3,5-di-O-mesyl-D-arabinofuranoside with sodium hydrogen selenide. Several X-ray diffraction analyses proved the structures of the products.
Synthesis of salacinol
Abstract Salacinol, a new type of α-glucosidase inhibitor discovered from the antidiabetic herb, was synthesized for the first time. Under the strategy that salacinol would be synthesized by the coupling reaction between 1,4-epithio- d -arabinitol and the cyclic sulfate of an erythritol derivative, the model coupling reactions between tetrahydrothiophene and versatile cyclic sulfate derivatives were undertaken. These experiments indicated that the 1,3-diol of the cyclic sulfate should be protected with the isopropylidene group, otherwise, even the benzylidene-protected cyclic sulfate decomposed during the reaction. Thus, the salacinol was synthesized using the cyclic sulfate of 1,3- O -isopypropylidene- d -erythritol. The resulting coupling product was deisopropylidenated to afford salacinol. A diastereomer of salacinol was also synthesized.
De novo highly stereocontrolled synthesis of 2,6-dideoxy sugars by use of 2,6-anhydro-2-thio sugars
Abstract Representative 2,6-dideoxy sugars, l -cladinose ( 1 ), l -mycarose ( 2 ), l -oleandrose ( 3 ), l -olivose ( 4 ), and all of their C-3 epimers, 2,6-dideoxy-3- C -methyl-3- O -methyl- l - arabino -hexopyranose ( 26 ), 2,6-dideoxy-3- C -methyl- l - arabino -hexopyranose ( l -olivomycose) ( 27 ), 2,6-dideoxy-3- O -methyl- l - ribo -hexopyranose ( l -cymarose) ( 32 ), and 2,6-dideoxy- l - ribo -hexopyranose ( l -digitoxose) ( 33 ) have been stereospecifically synthesized through a highly stereoselective addition of a nucleophilic reagent to the C-3 carbonyl groups of methyl 2,6-anhydro-4- O -benzyl-2-thio-α- l - arabino -hexopyranosid-3-ulose ( 11 ) or methyl 2,6-anhydro-4- O -benzyl-2-thio-β- l - arabino -hexopyranosid-3-ulose ( 12 ) possessing 2,6-anhydro-2-thio structures. Anomers 11 and 12 were both prepared in stereocontrolled fashion by treatment of a common intermediate, methyl 2,6-anhydro-4- O -benzyl-3- O -tetrahydropyranyl-2-thio-α- l -altropyranoside ( 8 ) with Lewis acids in methanol followed by oxidation.