A concise and stereoselective synthesis of iminosugar alkaloidsfrom α-Chloroaldehydes

Iminosugars have generated much attention in recent years as targets for the potential therapeutic treatment of a wide range of illnesses (e.g. cancer, HIV, diabetes, liposomal storage disorders, etc). Not surprisingly, the development of new synthetic methods towards iminosugars is of great interest to synthetic chemists. Previous synthetic strategies rely on carbohydrate starting materials (e.g. chiral pool synthesis) and are limited in their ability to produce stereoisomers or analogues, limiting their application to target-specific syntheses. We propose it is more advantageous to develop a method such that many stereoisomers and analogues can be synthesized from a common intermediate. This thesis describes a general, concise, and stereoselective method for the preparation of iminosugar alkaloids from non-carbohydrate starting materials. The method reported herein involves the diastereoselective nucleophilic addition of propargylamines to α-chloroaldehydes, followed by a domino epoxidation-cyclization sequence providing 2,5-dihydropyrrole intermediates that upon dihydroxylation provides iminosugar natural products in good overall yield and optical purity.