Merging Heterocyclic Chemistry and Biocatalysis in One-Pot Processes through Compartmentalization of the Reaction Steps

Nadine Zumbrägel; Harald Gröger

doi:10.3390/bioengineering5030060

Merging Heterocyclic Chemistry and Biocatalysis in One-Pot Processes through Compartmentalization of the Reaction Steps

Bioengineering (Basel). 2018 Aug 1;5(3):60. doi: 10.3390/bioengineering5030060.

Authors

Nadine Zumbrägel¹, Harald Gröger²

Affiliations

¹ Chair of Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany. nadine.zumbraegel@uni-bielefeld.de.
² Chair of Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany. harald.groeger@uni-bielefeld.de.

Abstract

A proof of concept for a one-pot process merging a heterocycle formation by a classical chemical approach at basic conditions with a biocatalytic reduction, running at neutral pH conditions, is reported. A crucial component for this process is the compartmentalization of the single reactions by the use of polydimethylsiloxane thimbles. This process was applied successfully towards an asymmetric synthesis of (S)-2,2,3-trimethyl-1-thia-4-azaspiro[4.4]nonane, leading to excellent enantioselectivities of 99% enantiomeric excess (ee).

Keywords: Asinger-type multi-component reaction; asymmetric synthesis; biocatalysis; cascades; compartmentalization; heterocycles.