Catalyst-Controlled Transannular Polyketide Cyclization Cascades: Selective Folding of Macrocyclic Polyketides

Area of Science:

• Organic Chemistry
• Biomimetic Synthesis
• Catalysis

Background:

• Polyketides are complex natural products with diverse biological activities.
• Current synthetic methods often face challenges in controlling stereochemistry and scaffold diversity.
• Macrocyclic substrates offer advantages in stability and conformational control for synthesis.

Purpose of the Study:

• To describe a novel biomimetic synthesis of aromatic polyketides.
• To utilize catalyst-controlled transannular cyclization cascades for efficient scaffold generation.
• To emulate key β-keto-processing steps found in natural polyketide biosynthesis.

Main Methods:

• Employing macrocyclic substrates with enhanced stability.
• Utilizing catalyst-controlled transannular cyclization cascades.
• Investigating selective formation of aromatic polyketide scaffolds.

Main Results:

• Successfully transformed macrocyclic substrates into distinct polyketide scaffolds.
• Achieved selective synthesis of aromatic polyketides via transannular cyclizations.
• Demonstrated control over folding and oxygenation patterns, mimicking biosynthesis.

Conclusions:

• Catalyst-controlled transannular cyclizations provide an efficient route to aromatic polyketides.
• This biomimetic approach offers a powerful strategy for accessing complex polyketide structures.
• The method effectively emulates crucial steps in natural polyketide biosynthesis.