A Biocatalytic Platform for the Synthesis of Enantiopure Propargylic Alcohols and Amines

Abstract

Propargylic alcohols and amines are versatile building blocks in organic synthesis. We demonstrate a straightforward enzymatic cascade to synthesize enantiomerically pure propargylic alcohols and amines from readily available racemic starting materials. In the first step, the peroxygenase from Agrocybe aegerita converted the racemic propargylic alcohols into the corresponding ketones, which then were converted into the enantiomerically pure alcohols using the ( R )-selective alcohol dehydrogenase from Lactobacillus kefir or the ( S )-selective alcohol dehydrogenase from Thermoanaerobacter brokii . Moreover, an enzymatic Mitsunobu-type conversion of the racemic alcohols into enantiomerically enriched propargylic amines using ( R )-selective amine transaminase from Aspergillus terreus or ( S )-selective amine transaminase from Chromobacterium violaceum was established. The one-pot two-step cascade reaction yielded a broad range of enantioenriched alcohol and amine products in 70–99% yield.

Considerations for the Scale‐up of in vitro Transaminase‐Catalyzed Asymmetric Synthesis of Chiral Amines

“…Essentially, a stirred batch reactor is a large vessel with a mechanical stirrer as depicted in Figure 1. Figure 1 includes a stirrer with two Rushton impellers as well as baffles on the inner walls to ensure proper mixing and a heating/ [191] cooling jacket with coolant inlet and outlet for temperature control. Generally, a batch reaction is run by addition of substrate and enzyme through the inlet in the top.…”

A Novel Unspecific Peroxygenase from Galatian Marginata for Biocatalytic Oxyfunctionalization Reactions

“…Also recombinant expression of UPOs in prokaryotic hosts such as Escherichia coli is possible [34][35]. Other research groups world-wide have accepted the challenge on broadening the scope of UPOs available for organic oxyfunctionalization reactions [36][37][38][39][40][41].…”

Synthesis of Enantioenriched Sulfoxides by an Oxidation‐Reduction Enzymatic Cascade

“…In contrast, peroxyzymes use partially reduced H 2 O 2 as an oxygen‐ and electron‐source and have also been demonstrated as useful catalysts in enantioselective oxidation of sulfides (Scheme 1B), in which the reaction scheme is significantly simplified. In particular, the unspecific peroxygenases from Agrocybe aegerita ( Aae UPO) [11] and chloroperoxidase from Caldariomyces fumago ( Cfu CPO) have shown excellent enantioselectivity in the asymmetric sulfoxidation of aryl alkyl sulfoxides [12] . However, as heme‐dependent enzymes, both Cfu CPO and Aae UPO show high sensitivity against the oxidant H 2 O 2 .…”