Concise Total Synthesis of (+)-Aphanorphine
Concise Total Synthesis of (+)-Aphanorphine: C. Wang, Y. Guan
Synlett 2021, 32, DOI: 10.1055/s-0037-1610769
Aphanorphine is a chiral tricyclic benzazepine alkaloid – structurally similar to natural and synthetic analgesic benzomorphan alkaloids, such as morphine – that was first isolated from natural sources in 1988. Although several strategies have been developed to construct the tricyclic benzazepine motif of aphanorphine, it remains an attractive and important synthetic target. Recently, the group of Professor Yukun Guan from Yantai University (P. R. of China) described a new approach for synthesizing the (+)-enantiomer of the title compound, relying on a key Pd-catalyzed intermolecular trimethylenemethane [3+2] cycloaddition to form the nitrogen-containing ring and a Co-catalyzed radical cyclization to close the central cyclohexyl ring.
Professor Guan said: “A six-step asymmetric total synthesis of (+)-aphanorphine was developed by our lab. We hope our effort can promote further medicinal chemistry research on aphanorphine.”