Total Synthesis Blog

Today, total synthesis of tetracyclic non-natural alkaloid (-)-Lycoricidine. Its enantiomer, (+)-Lycoricidine occurs in plants of the genus Amaryllidaceae (for example in the bulbs of narcissi):

The lycorine-type alkaloids exhibit wide spectrum of biological activities like carcinostatic and antiviral properties. The structure of (-)-Lycoricidine is shown below:

The plan of total synthesis includes application of certain cis-1,2-dihydrocatechols as starting material because of their microbiological availability. Retrosynthesis of target molecule is following:

The synthesis is very interesting, especially steps connected with conversion of stereochemistry in cyclohexene ring. Application of Overman rearrangement was tricky. It’s also interesting that the Suzuki-Miyaura cross-coupling and lactamization step occur nearly simultaneously.

For more information see: M. Matveenko, O. J. Kokas, M. G. Banwell, A. C. Wills, Organic Lett., 2007, 9, 3683.