Asymmetric Synthesis of (+)-Hinokinin, (+)-Dihydrocubebin and Cubebin Dimethyl Ether, a New Lignan from Phyllanthus niruri

The asymmetric synthesis of the new lignan cubebin dimethyl ether was accomplished in eight steps with an overall yield of 40 %. In addition, the known lignans (+)-hinokinin and (+)-dihydrocubebin were synthesized by this route. Our approach involves the highly diastereoselective and enantioselective (de ≥ 98 %, ee ≥ 98 %) construction of a trans-substituted 2,3-dibenzylbutyrolactone through an asymmetric Michael addition of an enantiopure lithiated aminonitrile to 5H-furan-2-one