Reactivity and Selectivity of Iminium Organocatalysis Improved by a Protein Host

Angewandte Chemie
Alexander R NödlingLouis Y P Luk

Abstract

There has been growing interest in performing organocatalysis within a supramolecular system as a means of controlling reaction reactivity and stereoselectivity. Here, a protein is used as a host for iminium catalysis. A pyrrolidine moiety is covalently linked to biotin and introduced to the protein host streptavidin for organocatalytic activity. Whereas in traditional systems stereoselectivity is largely controlled by the substituents added to the organocatalyst, enantiomeric enrichment by the reported supramolecular system is completely controlled by the host. Also, the yield of the model reaction increases over 10-fold when streptavidin is included. A 1.1 Å crystal structure of the protein-catalyst complex and molecular simulations of a key intermediate reveal the chiral scaffold surrounding the organocatalytic reaction site. This work illustrates that proteins can be an excellent supramolecular host for driving stereoselective secondary amine organocatalysis.

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Citations

Dec 24, 2018·Angewandte Chemie·Clemens MayerGerard Roelfes
Jun 12, 2019·Nature·Adam Nelson
May 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nicolò SantiLouis Y P Luk
Nov 6, 2020·Chemical Communications : Chem Comm·Prasun Mukherjee, Debabrata Maiti
Jan 15, 2021·Organic & Biomolecular Chemistry·Beatriz de Pina MarizAna Sofia Pina
Jan 27, 2021·Chemical Communications : Chem Comm·Nicolò SantiLouis Y P Luk
Feb 2, 2021·Science Advances·Tobias VornholtMarkus Jeschek
Jan 6, 2021·Chembiochem : a European Journal of Chemical Biology·Horst LechnerBirte Höcker
Jun 26, 2021·ACS Catalysis·Reuben B Leveson-GowerGerard Roelfes
Sep 12, 2019·Journal of the American Chemical Society·Shuke WuThomas R Ward
Nov 27, 2021·Organic & Biomolecular Chemistry·Alexander R NödlingLouis Y P Luk

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Methods Mentioned

BETA
protein crystallography

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