3,6-Thioanhydro sugar derivatives. An enantiospecific synthesis of (2R,3R,4S)-3-benzyloxy-4-hydroxy-2-[(R)-1-benzyloxy-4-hydroxybutyl]thiolane as the key intermediate for thioswainsonine [1]

Article abstract of DOI:10.1002/jhet.5570330440

Methyl 2-O-benzyl-3,6-thioanhydro-α-D-mannopyranoside (9) was obtained in eight steps from the commercially available methyl α-D-glucopyranoside. Compound 9 was transformed into (2R,3R,4S)-3-benzyloxy-4-hydroxy-2-[(R)-1-benzyloxy-4-hydroxybutyl]thiolane (14) by acid hydrolysis of its 2,4-di-O-benzyl derivative 10 followed by reaction of the not isolated 2,4-di-O-benzyl-3,6-thioanhydro-D-mannose (11) with ethoxycarbonylmethylenetriphenylphosphorane to give an ≈ 1:1 E/Z mixture of the corresponding α,β-unsaturated ester (12). Finally, catalytic hydrogenation of 12 to ethyl (R)-4-benzyloxy-4-[(2'R,3'R,4'S)-3'-benzyloxy-4'-hydroxythiolan-2'-yl]butanoate (13) and subsequent reduction with lithium aluminum hydride gave the title compound 14.