Divergent Synthesis of Bicyclic Iminosugars: Preparation of (−)‐Swainsonine‐Based Alkaloids and Their Inhibition Study towards α‐Human Mannosidases

A divergent and concise route to synthesize bicyclic iminosugars, especially polyhydroxylated pyrrolizidine and indolizidine‐based molecules, was described. Six natural product‐like bicyclic alkaloids including (−‐Swainsonine were conveniently prepared through this straightforward method. The key steps are diastereoselective allylation, ring size manipulation through hydroboration‐oxidation strategy and systematic installation of the amino functionality at the C8 position using nitrone chemistry. These Swainsonine analogues were applied for inhibition study against both α‐hLM and α‐hGMII. Interestingly, the C8 hydroxyl group with proper orientation plays a crucial role for inhibitory activities. The compounds possessing the C8 amino group drastically decrease their inhibitory activities. Indolizidine alkaloid: A divergent synthesis of Swainsonine analogues using diasteroselectivity, ring size manipulation and nitrone chemistry is developed. This expeditious and flexible strategy allows us to increase the scope of chemical space of bicyclic iminosugars and further test their abilities to inhibit disease related enzyme such as α‐mannosidases.