Efficient synthesis for each of the eight stereoisomers of the iminosugars lentiginosine and 1,4-dideoxy-1,4-imino-D-arabinitol (DAB)

Abstract

Herein, we describe the efficient, diastereoselective syntheses of the iminosugars 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) 1b, lentiginosine 3a, and the seven stereoisomers of each of these iminosugars starting from 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 with yields ranging from 38 % to 68 % for the DAB and isomers 1a-1h and from 44 % to 89 % for the lentiginosine and isomers 3a-3h. We also report the syntheses of the eight stereoisomers of the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 from commercially available sugars. Key to the iminosugar syntheses is a single multistep reaction that converts the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 to a vinyl pyrrolidine through a one-pot zinc mediated reductive elimination, followed by a reductive amination and finally an intramolecular nucleophilic substitution. Strategic selection of the amine utilized in the reductive amination and the functionalization of the intermediate carbon-carbon double bond provides access to a vast array of iminosugars.