A concise total synthesis of (±)-trigonoliimine B

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Hexacyclic alkaloids represent a class of complex natural products with potential pharmacological activities.
• Efficient synthetic routes are crucial for accessing and studying these molecules.

Purpose of the Study:

• To develop a concise and efficient total synthesis of Trigonoliimine B.
• To explore novel synthetic methodologies for constructing complex alkaloid frameworks.

Main Methods:

• A seven-step synthesis starting from simple materials.
• Utilized an α-isocyanoacetate as a glycine template for α,α-disubstituted α-amino ester synthesis.
• Employed an unprecedented Bischler-Napieralski reaction in sulfolane for seven-membered ring construction.

Main Results:

• Successful synthesis of Trigonoliimine B in seven steps.
• Demonstrated the utility of the α-isocyanoacetate strategy for creating highly substituted amino esters.
• Established sulfolane as an effective solvent for a novel Bischler-Napieralski reaction yielding an exo-imine.

Conclusions:

• The developed synthetic route provides efficient access to Trigonoliimine B.
• The study highlights a versatile strategy for constructing complex polycyclic systems.
• The novel application of the Bischler-Napieralski reaction expands synthetic possibilities in alkaloid chemistry.