Workpackage 1: Enantiopure 1,2-aminoalcohols from achiral substrates

Workpackage Leader: Prof. Dr. Anett Schallmey
Lead beneficiary: TU Braunschweig
Participating Partners: Enzymicals, Viazym, TU Delft
Start month: 7 End month: 42

Description of work and role of partners

Two novel cascades for the synthesis of enantiomerically pure 1,2-aminoalcohols, important precursors of various pharmaceuticals such as β- blockers, will be established starting either from prochiral ketones or achiral alkenes. In the first case, α-haloketones will be synthesized from corresponding methylketones by chloroperoxidase catalysis and transformed into enantiopure (R and S) aminoalcohols by combining chemical azidation with enzymatic reduction of the keto group and chemical hydrogenation of the intermediate azidoalcohol. In cascade 2, epoxide formation from achiral alkenes will be realized either by cytochrome P450 monooxygenases leading to enantioenriched epoxides or by a lipase together with H2O2 resulting in racemic epoxides. Afterwards, epoxide ring opening with azide will be performed by halohydrin dehalogenases yielding again 1,2-azidoalcohols which will be reduced chemically with help of a Pd-catalyst. Hence, both cascades involve the combination of enzymes with a chemical catalyst for which a new micro-compartimentalization concept will be established. This should avoid catalyst incompatibility and facilitate a one-pot strategy for both cascades.

Objectives

    1.) Assembly of novel two-enzyme cascades in combination with a chemical catalyst.
    2.) Avoiding catalyst incompatibility by micro-compartimentalization.

The Biocascades Project is a joint collaboration among the following university and industrial partners