A general catalytic reaction sequence to access alkaloid-inspired indole polycycles

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Indole and oxindole scaffolds are crucial in biologically active molecules.
• Developing efficient synthetic routes to complex heterocycles is essential for drug discovery.
• Existing methods for synthesizing these scaffolds can be lengthy or low-yielding.

Purpose of the Study:

• To develop a novel, efficient catalytic two-step reaction sequence.
• To access complex heterocyclic frameworks based on indole/oxindole scaffolds.
• To synthesize analogues of the alkaloid harmicine.

Main Methods:

• The study employed a catalytic Pictet-Spengler cyclization.
• A subsequent Au(I) catalyzed intramolecular hydroamination of acetylenes was performed.
• A cascade polycyclization of a designed β-carboline with a 1,5-enyne group was utilized.

Main Results:

• A range of complex heterocyclic frameworks were successfully synthesized.
• The reaction sequence proved effective for accessing biorelevant indole/oxindole scaffolds.
• Analogues of the alkaloid harmicine were obtained via cascade polycyclization.

Conclusions:

• The developed two-step sequence is a powerful tool for constructing complex heterocycles.
• This methodology offers an efficient route to valuable indole/oxindole-based compounds.
• The findings contribute to the synthesis of potential therapeutic agents.