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Issue 46, 2016
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Catalytic enantioselective acyl transfer: the case for 4-PPY with a C-3 carboxamide peptide auxiliary based on synthesis and modelling studies

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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.

Graphical abstract: Catalytic enantioselective acyl transfer: the case for 4-PPY with a C-3 carboxamide peptide auxiliary based on synthesis and modelling studies

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Supplementary files

Article information


Submitted
09 Sep 2016
Accepted
28 Oct 2016
First published
04 Nov 2016

Org. Biomol. Chem., 2016,14, 10914-10925
Article type
Paper

Catalytic enantioselective acyl transfer: the case for 4-PPY with a C-3 carboxamide peptide auxiliary based on synthesis and modelling studies

R. E. Cozett, G. A. Venter, M. R. Gokada and R. Hunter, Org. Biomol. Chem., 2016, 14, 10914
DOI: 10.1039/C6OB01991A

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