Stereocontrolled synthesis of four diastereomeric C-aryl manno- and talofuranosides

Abstract

In a chiral-pool synthesis starting from D-mannono-1,4-lactone 1a, the four diastereomeric C-aryl furanosides (1S,4R)-4a, (1S,4S)-4b, (1R,4R)-4c, and (1R,4S)-4d were obtained in a stereocontrolled manner. The key steps of the synthetic pathway comprise a stereoselective reduction of the diastereomeric hemiketals (4R)-2a and (4S)-2b as well as a stereospecific cycloetherification of the resulting diols (1R,4R)-5a, (1S,4R)-5c, and (1S,4S)-5d. This ring closure which led to the desired C-glycosides was achieved by a Mitsunobu reaction or by preparing the 1-O-benzoyl-4-O-methylsulfonyl derivative 7 which was then treated with sodium methoxide. Final hydrolysis of the 5,6-O-isopropylidene protecting group led to the diastereomeric diols (1S,4R)-4a, (1S,4S)-4b, (1R,4R)-4c, and (1R,4S)-4d, representing versatile building blocks for further synthetic transformations.