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

桥式双环化合物由于其构象刚性和sigma-对称性而成为立体选择合成天然产物的有效原料之一。因此，在本研究项目中，我们开发了用于合成生物活性生物碱的多用途手性构建块的不对称合成方法，该方法基于氮桥联双环“叉头”酮的不对称裂解，根据Koga的协议得到顺式2,5-二取代吡咯烷、顺式2,6-二取代和顺式3,5-二取代哌啶环体系。结果，我们实现了(+)-二氢pinidine， (-)-pinidine的二氢化合物，(+)- monmonorine I，法老蚂蚁的一种痕量信息素，和(-)-吲哚嗪223AB的全合成。此外，我们设计了一种sigma对称的环交乙二醇，并研究了它通过脂肪酶催化羟基分化转化为同手性酮。酮的裂解得到了一个高度功能化的3-哌啶醇。

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.