The First Enantioselective Total Synthesis of (−)-<i>trans</i>-Dihydronarciclasine

A feasible and enantioselective total synthesis of (−)-<i>trans</i>-dihydronarciclasine [(−)-<b>1</b>], a highly biologically active alkaloid, was devised starting from vanillin (<b>8</b>). The key step of this new synthesis was an asymmetric, organocatalytic Michael addition, in which an optically active nitropentanone [(−)-<b>13</b>] was obtained from a butenone derivative (<b>12</b>). Excellent enantioselectivity (>99% ee) was achieved using the (8<i>S</i>,9<i>S</i>)-9-amino­(9-deoxy)­epiquinine (<b>16</b>) organocatalyst. The target molecule can be prepared in 13 steps from compound (−)-<b>13</b>. The total synthesis has provided a facile and first access to the <i>ent</i>-form of naturally occurring (+)-<i>trans</i>-dihydronarciclasine, a highly potent cytostatic alkaloid