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Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
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Concise Synthesis of Tetrazole Macrocycle.
Eman M M Abdelraheem1,2, Michel P de Haan1, Pravin Patil1
1Department of Drug Design, University of Groningen , A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Organic Letters
|September 14, 2017
Summary
A new two-step synthesis creates tetrazole macrocycles efficiently. This method allows for easy variation of substituents at three positions on macrocycles ranging from 11 to 19 members.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Synthetic Chemistry
Background:
- Macrocycles are important scaffolds in medicinal chemistry.
- Efficient synthesis of diverse macrocycles remains a challenge.
Purpose of the Study:
- To develop a concise and versatile method for synthesizing tetrazole-containing macrocycles.
- To enable independent variation of substituents at multiple positions within the macrocycle.
Main Methods:
- A two-step synthesis involving chemoselective amidation followed by a tetrazole-forming Ugi reaction.
- Utilized amino acid-derived isocyanocarboxylic acid esters and symmetrical diamines.
- Formation of α-isocyano-ω-amines intermediates.
Main Results:
- Successfully synthesized 11-19-membered tetrazole-containing macrocycles.
- Demonstrated a straightforward route from accessible starting materials.
- Achieved independent variation of substituents at three distinct positions.
Conclusions:
- The presented two-step strategy offers a rapid and flexible approach to diverse tetrazole macrocycles.
- This method is advantageous for accessing complex macrocyclic structures with tunable properties.
- Facilitates the exploration of novel macrocyclic compounds for various applications.
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