Concise syntheses of eburnane indole alkaloids

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Eburnane alkaloids are a class of complex natural products with potential pharmaceutical applications.
• Developing efficient synthetic routes to these molecules is crucial for further biological investigation.

Purpose of the Study:

• To achieve the asymmetric divergent syntheses of five C20 ethyl oxo-functionalized eburnane alkaloids.
• To establish a novel synthetic strategy utilizing photoredox catalysis for complex alkaloid assembly.

Main Methods:

• Employing a photoredox catalytic nitrogen-centered radical cascade reaction as the key step.
• Utilizing this cascade for the regioselective and stereoselective construction of the B, C, and D rings.
• Installing the C21 chirality of the eburnane alkaloid skeleton in a one-pot procedure.

Main Results:

• Successful synthesis of (-)-eburnaminol (5), (+)-larutenine (6), (-)-terengganensine B (7), (-)-strempeliopine (8), and (-)-terengganensine A (9).
• Demonstrated the efficacy of the photoredox catalytic cascade in constructing the intricate eburnane core.
• Achieved high levels of regioselectivity and stereoselectivity in the ring formations and chirality installation.

Conclusions:

• The developed synthetic methodology provides an efficient route to valuable eburnane alkaloids.
• The photoredox catalytic radical cascade reaction is a powerful tool for constructing complex polycyclic systems.
• This work expands the synthetic accessibility of eburnane alkaloids for potential drug discovery efforts.