Model studies directed toward the alkaloid mersicarpine utilizing a Rh(II)-catalyzed insertion/cycloaddition...

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• The alkaloid mersicarpine presents a complex polycyclic structure with multiple stereocenters.
• Efficient synthetic routes are needed to access mersicarpine and its analogs for further study.

Purpose of the Study:

• To develop a novel rhodium(II)-catalyzed cascade reaction for the synthesis of the alkaloid mersicarpine.
• To construct the tricyclic core of mersicarpine with high yield and stereoselectivity.

Main Methods:

• Rhodium(II)-catalyzed carbenoid insertion/cyclization/cycloaddition cascade reaction.
• Utilized α-diazo dihydroindolinones as starting materials.
• Acid-induced hydrolysis and subsequent multi-step transformations.

Main Results:

• The cascade reaction of α-diazo dihydroindolinone 21 yielded cycloadduct 22 with high diastereoselectivity.
• Successfully constructed the tricyclic core of mersicarpine.
• The reaction rapidly assembled a polycyclic system with three new stereocenters and three continuous quaternary carbons.

Conclusions:

• The developed cascade reaction is a powerful tool for the rapid and stereoselective synthesis of complex polycyclic systems.
• This approach provides a viable route towards the synthesis of mersicarpine and related alkaloids.
• Further steps involving reduction and reductive cyclization are planned for the synthesis of demethylmersicarpine.