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07:11
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
A new and useful method for the macrocyclization of linear peptides
Allyn T Londregan1, Kathleen A Farley, Chris Limberakis
1CVMED Medicinal Chemistry, Pfizer Inc., Eastern Point Road, Groton, Connecticut 06340, USA. allyn.t.londregan@pfizer.com
Organic Letters
|May 23, 2012
Summary
A novel peptide macrocyclization method utilizes natural amino acid side chains and a PyBroP-activated pyridine-N-oxide-carboxamide. This efficient and mild procedure offers broad applicability in synthesizing complex cyclic peptides.
Area of Science:
- Organic Chemistry
- Peptide Chemistry
- Medicinal Chemistry
Background:
- Peptide macrocyclization is crucial for developing therapeutics.
- Existing methods often require harsh conditions or complex protecting groups.
Purpose of the Study:
- To develop a mild, efficient, and broadly applicable method for peptide macrocyclization.
- To demonstrate the utility of PyBroP-activated pyridine-N-oxide-carboxamide in intramolecular cyclization.
Main Methods:
- Intramolecular reaction of tyrosine, lysine, and histidine side chains with activated pyridine-N-oxide-carboxamide.
- Utilized the phosphonium salt, PyBroP, for selective activation.
- Characterization using standard analytical techniques.
Main Results:
- Successful macrocyclization of linear peptides using natural amino acid side chains.
- Demonstrated mild, rapid, and efficient reaction conditions.
- Synthesized a novel aza-variant of the vancomycin C-O-D ring system.
Conclusions:
- The described procedure provides a versatile new route for peptide macrocyclization.
- The method is efficient and compatible with natural amino acid functionalities.
- Potential applications in drug discovery and synthesis of complex natural products.
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