Efficient Synthesis of Macrocyclic Peptides

  • Author: Angewandte Chemie International Edition
  • Published Date: 11 December 2019
  • Source / Publisher: Angewandte Chemie International Edition/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
thumbnail image: Efficient Synthesis of Macrocyclic Peptides

Macrocyclic peptides are useful components of several pharmaceuticals. However, their creation is challenging because intermolecular reactions can generate unwanted dimers and oligomers. Conventional macrocyclization reactions are, thus, carried out at high dilution and with long reaction times to promote ring-closing reactions instead of these side reactions.


Monika Raj, Auburn University, AL, USA, and colleagues have developed a method for the synthesis of macrocyclic peptides. The so-called "CyClick" reaction is selectively intramolecular and creates cyclic peptides in high yields without side products. The cyclization of linear peptides is performed in a 1:1 mixture of water and N,N-dimethylformamide (DMF) in the presence of 4-dimethylaminopyridine (DMAP) at room temperature. The reaction first gives a cyclic imine intermediate (pictured in the center below), which undergoes another ring-closing to form a stable 4-imidazolidinone-fused cyclic peptide  A new chiral center is generated in this process with high stereoselectivity.

 

 

The CyClick reaction can be carried out in one pot and under mild conditions. A variety of cyclic peptides with different ring sizes (12- to 24-membered) and amino acid compositions are accessible. High conversions are reached even at 25 times the concentration of current methods. The researchers believe that this process could streamline the synthesis of macrocyclic peptides for pharmaceutical applications.


 

 

Article Views: 1524

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

Bookmark and Share

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission. more


CONNECT:

ChemistryViews.org on Facebook

ChemistryViews.org on Twitter ChemistryViews.org on YouTube ChemistryViews.org on LinkedIn Sign up for our free newsletter


Magazine of Chemistry Europe (16 European Chemical Societies)published by Wiley-VCH