Research Article

Microwave Assisted Aza-michael Additions Towards β-amino Acids

Author(s):

Fan Yinqi and Matziari Magdalini*   Pages 166 - 177 ( 12 )

Abstract:

Background: β-amino acids are non-natural amino acids, where the amino group is attached to the β-carbon instead of the α-carbon. Peptides containing β-amino acids present with particular secondary structures and remarkable chemical and biological properties. β-peptides are used as peptidomimetics, based on the resistance to hydrolysis in vivo, with various important applications in the field of Medicine.

Methods: Several synthetic methods have appeared in recent years, with the Aza- Michael conjugate addition reactions, being a very effective approach towards β-amino acids. Microwave irradiation mediated reactions have also attracted much interest since they significantly improve the reaction yields while reducing the reaction time and avoiding by-products formation. The aim of this project has been the development of a reliable and general synthetic methodology towards β² and β³ amino acids with the use of conjugate additions of N-nucleophiles to substituted acrylate derivatives. The application of effective catalysts has been also examined here.

Results: The results show that the acrylate precursors of β² and β³ amino acids with side chains corresponding to Phe, Asp, Ile, Leu, Val, and Tyr have been synthesized successfully by using a one-pot Horner-Wadsworth-Emmons reaction, and they have been used for the addition of Nnucleophiles, with a study on conditions and yields optimization.

Conclusion: With the main challenge for β-amino acid synthesis being that there is still no general method to synthesize different types of β-amino acids corresponding to all-natural α-amino acids, the proposed synthetic methodology may offer this possibility.

Keywords:

β-amino acids, peptidomimetics, michael addition, microwave irradiation, horner-wadsworth-emmons reaction, acrylates.

Affiliation:

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