Synthesis of the C13-C27 Fragment of Madeirolide A Using Visible-Light-Promoted Radical Cyclization

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Natural Product Synthesis

Background:

• Madeirolide A is a complex marine macrolide with potential biological activities.
• Total synthesis provides access to complex natural products for further study.
• Efficient synthetic strategies are crucial for constructing intricate molecular architectures.

Purpose of the Study:

• To achieve a convergent synthesis of a significant fragment (C13-C27) of madeirolide A.
• To develop and apply novel stereocontrolled methods for constructing heterocyclic rings.
• To establish a robust late-stage coupling strategy for assembling complex molecules.

Main Methods:

• Visible-light-induced iridium-catalyzed radical cyclization for stereocontrolled formation of tetrahydrofuran (THF) and tetrahydropyran (THP) rings.
• Nickel-catalyzed decarboxylative cross-coupling for the late-stage union of key oxacyclic subunits.
• Convergent synthetic strategy to maximize efficiency and minimize steps.

Main Results:

• Successful synthesis of a fully elaborated C13-C27 fragment of madeirolide A.
• Stereocontrolled construction of both THF and THP rings was achieved.
• Efficient late-stage coupling of the two major subunits was demonstrated.

Conclusions:

• The developed synthetic route provides a reliable method for accessing a key fragment of madeirolide A.
• The application of visible-light-induced radical cyclization and nickel-catalyzed cross-coupling highlights their utility in complex molecule synthesis.
• This work contributes to the ongoing efforts in the total synthesis of madeirolide A and related natural products.