Research progress on the asymmetric total synthesis of lycorine

Lycorine is an alkaloid in the amaryllidaceae family, with multiple pharmacological activities such as anti-tumor, anti-inflammatory, and antiviral activity. Its structural skeleton is a tetracyclic galanthane ring bearing four consecutive chiral centers. The keys to the successful synthesis of lycorine lies in the selective introduction of aromatic rings into the cyclohexane skeleton, the efficient construction of nitrogen-containing bicyclic rings, the stereo-controlled synthesis of tetrasubstituted cyclohexanes, and the construction of double bonds. Therefore, in order to synthesize a variety of alkaloids with a lycorine skeleton, medicinal chemists and organic chemists are committed to developing more convenient and efficient synthetic methods, providing important fundamentals for structural diversity-oriented drug development. This review summarized the new progress in the asymmetric total synthesis of lycorine since 2000, in which five teams have developed different synthetic routes and each have their own advantages. They used the classic Michael addition reaction or Diels-Alder reaction, and the overall yield of the synthesis was improved, which reflects the creativity of different synthetic strategies in the synthesis of the complex natural product lycorine and is of great significance in the fields of organic chemistry and medicinal chemistry.