Design of Versatile Chiral Building Blocks via Asymmetric Cleavage of the Bridged Bicyclic Ketone and Its Applications to the Natural Product Synthesis

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We have focused our attention on the bridged bicyclic compound as one of the useful starting material for stereoselective synthesis of natural products because of its conformational rigidity and sigma-symmetry.Thus, in this research project, we have developed the asymmetric synthesis of versatile chiral building blocks for the synthesis of biologically active alkaloids based on the asymmetric cleavage of the nitrogen-bridged bicyclic 'fork head' ketone according to the Koga's protocol to afford cis-2,5-disubstituted pyrrolidine, cis-2,6-disubstituted, and cis-3,5- disubstituted piperidine ring systems.As a result, we acheived the total synthesis of (+)-dihydropinidine, the dihydro compound of (-)-pinidine, (+)-monomorine I, a trail pheromone of the pharaoh ant, and (-)-indolizidine 223AB.In addition, we designed a sigma-symmetric ring-crossed glycol and examined its transformation into a homochiral ketone via lipase-catalyzed differentiation of the hydroxyl. The cleavage of the ketone obtained furnished a highly functionalized 3-piperidinol.