Sequential one-pot cyclizations: concise access to the ABCE tetracyclic framework of strychnos alkaloids

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Strychnos alkaloids are a complex class of natural products with significant biological activities.
• The intricate tetracyclic ABCE framework presents a synthetic challenge.
• Efficient routes to this core structure are crucial for drug discovery and development.

Purpose of the Study:

• To develop a novel, sequential one-pot synthetic strategy.
• To access the ABCE tetracyclic framework of Strychnos alkaloids.
• To establish an efficient method for constructing complex alkaloid scaffolds.

Main Methods:

• A sequential one-pot biscyclization approach was employed.
• Silver triflate (AgOTf) mediated spirocyclization of an indole 3-carbinamide derivative.
• 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) induced intramolecular aza-Baylis-Hillman reaction.

Main Results:

• A stable spiroindolenine intermediate was successfully generated.
• An unprecedented intramolecular aza-Baylis-Hillman reaction was achieved in situ.
• The target tetracyclic product was obtained in a 70% isolated yield.

Conclusions:

• A facile and efficient sequential one-pot biscyclization route to the Strychnos alkaloid ABCE framework has been established.
• This methodology offers a streamlined approach for synthesizing complex polycyclic systems.
• The developed strategy holds potential for the synthesis of novel Strychnos alkaloid analogs.