Reaction Design for the Compartmented Combination of Heterogeneous and Enzyme Catalysis

Abstract

The combination of a heterogeneously catalyzed reaction with a biotransformation as a one-pot cascade process is an important strategy to reduce costs, time, and labor efforts in the production of chemicals from biogenic resources. Although one-pot cascade-type approaches generally result in more efficient chemical processes by reducing the number of workup operations needed and time consumed, the combination of different types of catalysts, both chemical and enzymatic, into a single reaction vessel often remains challenging. During our study, aimed at the direct synthesis of 2-keto-3-deoxy sugar acids as one intermediate toward biobased building blocks starting from the corresponding sugars by combining heterogeneous inorganic catalysis with enzyme catalysis, we encountered several incompatibility problems. These were overcome by a chemoenzymatic method in different compartments, which involves the gold-catalyzed direct oxidation by molecular oxygen and the subsequent conversion of the sugar acids through an enzymatic dehydration step. The described procedure represents an efficient synthesis route toward four different 2-keto-3-deoxy sugar acids and serves as a proof of concept for the combination of one-pot-incompatible catalysts under continuous flow.

Overcoming the Incompatibility Challenge in Chemoenzymatic and Multi‐Catalytic Cascade Reactions

“…Sieber et al. suggested a new route for their synthesis by the coupling of the chemical oxidation of sugars with an enzymatic dehydration step . Similar to the work of Gonzalez–Sabín and co‐workers (see above), the synthetic challenge was to achieve an oxidation under mild reaction conditions and the combination with an enzymatic step without intermediary steps for product recovery.…”

Substrate scope of a dehydrogenase from Sphingomonas species A1 and its potential application in the synthesis of rare sugars and sugar derivatives

“…Aldonic acids were prepared from their corresponding sugars by oxidation using a gold catalyst (J213 XI/D 0.5%, 0.5% Au on Al 2 O 3 powder, kindly provided by Evonik Industries, Germany). The procedure has been previously described for l ‐arabinose, d ‐xylose, d ‐galactose and d ‐glucose (Sperl et al ., ), as well as for d ‐ribose, d ‐lyxose, d ‐mannose, l ‐rhamnose and N ‐acetyl‐glucosamine (Mirescu and Prüße, ), and could be adapted for the oxidation of d ‐allose, d ‐altrose, d ‐talose, d ‐arabinose, d ‐erythrose, d ‐threose, 2‐deoxy‐ d ‐glucose and 3‐deoxy‐ d ‐glucose. The results can be found in the supporting information.…”

“…The keto-deoxy sugar KDG was obtained from D-gluconate using the enzyme dihydroxy-acid dehydratase from Sulfolobus solfataricus. This detailed procedure is described by Sperl et al (2016).…”

Non‐Conventional Media as Strategy to Overcome the Solvent Dilemma in Chemoenzymatic Tandem Catalysis

“…For chemo‐enzymatic tandem reactions, flow systems allow to conduct several steps at different temperatures, which is often a crucial advantage. Sieber et al . demonstrated the feasibility with the combination of a chemo‐catalyzed oxidation with an enzymatic dehydration in aqueous system for the synthesis of 2‐ketoacids from sugars (Scheme a).…”