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.
Preparation of methyl 2,3-di-O-mesyl-4,6-thioanhydro-α-d-galactopyranoside and methyl 2-O-mesyl-4,6-thioanhydro-α-d-gulopyranoside
Abstract Two 2-oxa-7-thiabicyclo[4.2.0]octane derivatives, 4 and 10, with the d -galacto and d -gulo configuration, respectively, were obtained from methyl α- d -glucopyranoside. The thietane cyclization involved a thio-Mitsunobu reaction resulting in a 6-thioacetate, which underwent selective base-catalyzed intramolecular nucleophilic substitution at a C-4 mesylate. The structureS of 4 and 10 were elucidated by X-ray diffraction analysis.
Preferential sulfonylation of methyl 2,6-di-O-mesyl-α-D-glucopyranoside
Abstract When equimolar ratios of mesyl chloride and methyl 2,6-di- O -mesyl-α- D -glucopyranoside were allowed to react in pyridine and the product resolved by preparative t.l.c., the 2,6-di-, 2,3,6-tri-, 2,4,6-tri-, and 2,3,4,6-tetra-mesyl esters were obtained in (0.5–0.6):1:(4–5):(1-2-1.4) molar ratio. Benzoylation of either the isolated 2,4,6-tri- O -mesyl ester or, more conveniently, the mixture from monomesylation gave the crystalline methyl 3- O -benzoyl-2,4,6-tri O -mesyl-α- D -glucopyranoside ( 8 ). As both of these trimesyl esters ( 7 and 8 ) are unreported, isolation of the benzoate established the 2,4,6-ester arrangement, and the 2,3,6-triester was prepared by standard methods. Treating methyl α- D -glucopyranoside with 3 molar equivalents of mesyl chloride and, subsequently, with 1 molar equivalent of benzoyl chloride, proved a convenient method for preparing the 3- O -benzoyl derivative in moderate yield. Monotosylation of methyl 2,6-di- O mesyl-α- D -glucopyranoside was not so definitive as mesylation, but a molar ratio of 1:2.8 for the 3- O -tosyl:4- O -tosyl product was derived from n.m.r. data. This work, when combined with literature reports, establishes that, in methyl α- D -glucopyranoside, the reactivity toward sulfonylation is 6-OH>2-OH>4-OH>3-OH.