A novel approach toward the synthesis of substituted piperidines and iminosugars

Polyhydroxylated piperidines, also known as iminosugars, have received much attention in the past few decades as potential drug leads and the development of new methods for their synthesis is therefore of considerable interest. The most common drawback to current iminosugar syntheses is their reliance on carbohydrate chemistry which involves multiple protecting group manipulations that render the synthesis laborious and target specific. In this thesis, a new and concise synthetic process for the synthesis of iminosugars is described. This synthesis employs, as the key step, an intramolecular inverse electron demand Diels-Alder reaction between a hydroxymethyl oxazole and enolate joined through a silicon tether. Remarkably, the synthesis of iminosugars can now be accomplished in a two-pot reaction sequence that initiates with 4-hydroxymethyl oxazole and provides an unnatural analogue of a biologically active iminosugar in good overall yield.