The Chemical Synthesis of the 1-C-Alkyl Substituted Pyrrolidine and Piperidine Iminosugar Natural Products and their Analogues

A review of the chemical synthesis of the 1-C-alkyl substituted pyrrolidine and piperidine iminosugar natural products and their analogues (where the alkyl chain comprises two or more carbons) is provided. These syntheses can be grouped into nine different synthetic strategies that share a common approach toward installing the alkyl substituent. These include nucleophilic addition to aldimines; Grignard additions to glycosylamines, cyclic imides, and carbohydrates; Weinreb ketone synthesis; nucleophilic addition to cyclic nitrones; the Overmann rearrangement; the allylation of hemiaminals; and the Petasis borono-Mannich reaction. The broussonetine alkaloids have proven popular synthetic targets to develop new synthetic methods and verify these target molecules' structures and stereochemistry.