A Highly Efficient and Stereocontrolled Synthesis of 2‐Deoxy‐1,5‐thioanhydro‐L‐hexitols from D‐Glycals in a Tandem Nucleophilic Displacement Reaction

Abstract

2-Deoxy-1,5-thioanhydro-L-hexitols have been synthesized in a concise sequence that includes: i) ring opening of glycals with aqueous mercury(II) acetate/sodium borohydride; ii) mesylation of the free hydroxy groups of the multifunctionalized open intermediates; and iii) S-heterocyclization by treatment with sodium sulfide. The thiosugar derivatives are obtained with a 60-80 % yield. Thus, D-glucal and D-galactal can be converted into the corresponding 2-deoxy-1,5-thioanhydro-L-hexitols, while L-rhamnal gives 3,4-di-O-benzyl-2,6-dide-

Glycals in Organic Synthesis: A Systematic Strategy for the Preparation of Uncommon Piperidine 1,2‐Dideoxy‐L‐azasugars and 2‐Deoxy‐1,5‐anhydro‐L‐hexitols

“…All the starting materials were prepared in one step from O ‐benzyl derivatives of glycals and glycosyl glycals according to our previously reported procedure25,29 by treatment with aqueous mercury(II) acetate/sodium borohydride in one reaction flask and on a large scale.…”

“…To test the efficiency of our strategy, we prepared the enantiomerically pure (3 R ,4 R ,5 R )‐3,4,6‐tris(benzyloxy)hexane‐1,5‐diol ( 2a ) and the corresponding (3 R ,4 S ,5 R ) diastereoisomer 2b , available from the corresponding D ‐glucal and D ‐galactal, respectively,25,29 and characterized by the presence of a primary and secondary alcohol (Scheme ). The intermediates 2a and 2b have a carbon skeleton with the required protected functionalities and the free hydroxy groups necessary for the introduction of the nitrogen atom in the right position to prepare the 1,5‐iminosugar derivatives.…”

“…Interestingly, (3 R ,4 R ,5 S )‐3,4‐bis(benzyloxy)hexane‐1,5‐diol ( 6 ), obtained from per‐ O ‐benzylated L ‐rhamnal,25,29 was easily converted into the unknown 3,4‐di‐ O ‐benzyl‐2,6‐dideoxy‐1,5‐imino‐ D ‐ xylo ‐hexitol ( 9 ) in 60 % yield via intermediates 7 and 8 , following the above procedure (Scheme ).…”

“…As part of our continuing exploitation of the reactivity and the usefulness of carbohydrate derivatives in organic synthesis,25 we herein describe a new and expeditious strategy for the synthesis of uncommon piperidine 1,2‐dideoxy‐ L ‐azasugars that allows access to these compounds in a few steps starting from readily available D ‐glycal derivatives. The versatility of this methodology was demonstrated by its application in disaccharide chemistry.…”

Design and synthesis of glycomimetics: Recent advances

“…Several methodologies have been developed for the preparation of thiosugars . Among the most recent examples, a general one‐pot synthesis of thiosugars 64 by double nucleophilic displacement from various alditol precursors 65 (with xylo‐, ribo‐, manno‐, gluco‐, galacto‐, and fuco‐configurations) was reported by Zhang et al (Figure A).…”