Synthesis of the naringinase inhibitors l-swainsonine and related 6-C-methyl-l-swainsonine analogues: (6R)-C-methyl-l-swainsonine is a more potent inhibitor of l-rhamnosidase by an order of magnitude than l-swainsonine

Efficient syntheses are reported of the α-l-rhamnosidase inhibitors l-swainsonine [(1R,2S,8S,8aS)-octahydroindolizine-1,2,8-triol], (6R)-C-methyl-l-swainsonine (1R,2S,6R,8S,8aS)-6-methyloctahydro-indolizine-1,2,8-triol, (6S)-C-methyl-l-swainsonine (1R,2S,6S,8S,8aS)-6-methyloctahydro-indolizine-1,2,8-triol and related 6-C-methyl hydroxycastanospermines [(1R,2S,6R,7R,8R,8aR)-6-methyl-octahydroindolizine-1,2,6,7,8-pentaol and (1R,2S,6S,8S,8aS)-6-methyloctahydro-indolizine-1,2,8-triol]. (6R)-C-Methyl-l-swainsonine [Ki = 0.032 μM] is a significantly more potent naringinase inhibitor than l-swainsonine [Ki = 0.45 μM].