A straightforward synthesis of tetrameric estrone-based macrocycles

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Supramolecular Chemistry

Background:

• Macrocycles are complex molecular architectures with significant applications in medicine and materials science.
• Estrone-derived scaffolds offer unique structural features for developing novel compounds.
• Efficient synthetic strategies are crucial for accessing complex macrocyclic structures.

Purpose of the Study:

• To develop a straightforward and efficient synthetic route to macrocycles incorporating multiple estrone-derived nuclei.
• To demonstrate the versatility of the developed method for natural product scaffold modification.

Main Methods:

• Sequential copper-catalyzed Huisgen azide-alkyne cycloaddition.
• Glaser-Eglington copper homocoupling reaction.
• Synthesis of macrocycles featuring four estrone-derived units.

Main Results:

• A facile and direct method for constructing tetra-estrone macrocycles was established.
• The sequential cycloaddition-homocoupling strategy proved highly efficient.
• The methodology is amenable to various natural product scaffolds, highlighting its broad applicability.

Conclusions:

• The developed sequential copper-catalyzed reaction sequence provides a robust approach to complex macrocycles.
• This method offers a simplified route to estrone-based macrocycles with potential applications in drug discovery and materials science.
• The efficiency and simplicity of the sequence make it valuable for modifying diverse natural product scaffolds.