Diazene Directed Modular Synthesis of Oligocyclotryptamines

Technology

This synthesis reaction is the first generalizable strategy for generating oligocyclotryptamines with complete stereochemical control. The reaction is facilitated by first synthesizing aryl-alkyl diazenes that serve as monomers that are then iteratively reacted to build the large oligocyclotryptamine molecules. Additionally, this system is modular, and the inventors describe successful synthesis of pure enantiomeric forms of five different oligocyclotryptamine molecules by simply switching diazene monomer choice.

Problem Addressed

Hexahydropyrroloindole alkaloids, including oligocyclotryptamines, are structurally complex, naturally occurring chemicals with a wide range of therapeutically relevant properties, including antibacterial, antifugal, anticancer, and analgesic activity. However, the biological activity of oligocyclotryptamines is highly dependent on the enantiomeric form of the molecule, and the rare oligocyclotryptamines found in nature exist as a mix of enantiomers. Additionally, the presence of multiple stereocenters makes chemical synthesis of pure enantiomers nearly impossible, and therefore, the potential therapeutic properties of oligocyclotryptamines have remained largely unexplored.

Advantages

• Efficient synthesis of biologically active oligocyclotryptamines
• Complete control of stereochemistry at all stereocenters
• Highly modular, generalizable synthesis that can be applied to synthesis of many different oligocyclotryptamine molecules

Publications

Lindovska, Petra, and Mohammad Movassaghi. "Concise Synthesis of (−)-Hodgkinsine, (−)-Calycosidine, (−)-Hodgkinsine B, (−)-Quadrigemine C, and (−)-Psycholeine via Convergent and Directed Modular Assembly of Cyclotryptamines." Journal of the American Chemical Society, 139 (2017): 17590-17596. doi: 10.1021/jacs.7b09929.