AI Article Synopsis
- A series of 4-PPY C-3 carboxamides with peptide side chains were created and tested for their ability to resolve chiral benzylic secondary alcohols.
- The design emphasized using a tryptophan residue to enhance π-stacking interactions, supported by structure-based modeling techniques.
- A specific catalyst with a LeuTrp-N-Boc side chain showed promising results, providing enantioselectivity values slightly over 10, highlighting the role of modeling in improving catalyst performance for potential large-scale applications.
Article Abstract
A series of 4-pyrrolidinopyridine (4-PPY) C-3 carboxamides containing peptide-based side chains have been synthesised and evaluated in the kinetic resolution of a small library of chiral benzylic secondary alcohols. A key design element was the incorporation of a tryptophan residue in the peptide side chain for promoting π-stacking between peptide side chain and the pyridinium ring of the N-acyl intermediate, in which modelling was used as a structure-based guiding tool. Together, a catalyst containing a LeuTrp-N-Boc side chain (catalyst 8) was identified that achieved s-values up to and in slight excess of 10. A transition-state model based on the modelling is proposed to explain the origin of enantioselectivity. This study establishes the usefulness of modelling as a structure-based guiding tool for enantioselectivity optimization as well as the potential for developing scalable peptide-based DMAP-type catalysts for large-scale resolution work.
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| http://dx.doi.org/10.1039/c6ob01991a | DOI Listing |
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