The First Enantioselective Total Synthesis of (-)-trans-Dihydronarciclasine
Gábor Varró1, László Hegedűs2, András Simon3
1Department of Organic Chemistry and Technology, Budapest University of Technology and Economics , Budafoki út 8, H-1111 Budapest, Hungary.
Abstract:
A feasible and enantioselective total synthesis of (-)-trans-dihydronarciclasine [(-)-1], a highly biologically active alkaloid, was devised starting from vanillin (8). The key step of this new synthesis was an asymmetric, organocatalytic Michael addition, in which an optically active nitropentanone [(-)-13] was obtained from a butenone derivative (12). Excellent enantioselectivity (>99% ee) was achieved using the (8S,9S)-9-amino(9-deoxy)epiquinine (16) organocatalyst. The target molecule can be prepared in 13 steps from compound (-)-13. The total synthesis has provided a facile and first access to the ent-form of naturally occurring (+)-trans-dihydronarciclasine, a highly potent cytostatic alkaloid.
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