Radical-Based Route to Functionalized Tetralin: Formal Total Synthesis of (±)-Hamigeran B

Area of Science:

• Organic Synthesis
• Marine Natural Products Chemistry
• Medicinal Chemistry

Background:

• Hamigeran B is a marine natural product with demonstrated antiviral properties.
• Its complex tricyclic structure presents a significant synthetic challenge.
• Developing efficient synthetic routes is crucial for further biological evaluation and potential drug development.

Purpose of the Study:

• To establish a formal synthetic route to hamigeran B.
• To explore novel chemical transformations for constructing its unique molecular architecture.
• To provide a scalable method for accessing this antiviral compound.

Main Methods:

• Zinc(II)porphyrin-catalyzed photoredox radical cascade cyclization to form a functionalized tetralin intermediate.
• Catalyst-free benzylic radical bromination using N-bromosuccinimide (NBS) under visible-light irradiation.
• Samarium(II)-induced cyclization of a brominated tetralone precursor, potentially involving an orthoquinodimethane-like intermediate.

Main Results:

• Successful development of a formal synthetic route to hamigeran B.
• Demonstration of a novel zinc(II)porphyrin-catalyzed photoredox radical cascade for tetralin synthesis.
• Efficient catalyst-free benzylic bromination achieved using visible-light photoredox catalysis.
• Samarium(II)-mediated cyclization successfully formed the tricyclic core.

Conclusions:

• A viable synthetic strategy for hamigeran B has been achieved.
• The developed methods showcase innovative applications of photoredox catalysis and radical chemistry in complex molecule synthesis.
• This route provides access to hamigeran B for further antiviral research.