Resolution of 1,2-Diols by Enzyme-Catalyzed Oxidation with Anodic, Mediated Cofactor Regeneration in the Extractive Membrane Reactor:  Gaining Insight by Adaptive Simulation

Abstract

Oxidative racemic resolution of 1,2-diols is a method for the synthesis of enantiopure diols not easily accessed by reduction. The constraints generally found for oxidation to hydroxy ketones can be overcome by coupling various techniques. To circumvent product inhibition, a membrane reactor with solvent extraction of the lipophilic product was chosen. For the oxidative regeneration of NAD+ from NADH anodic oxidation mediated by ABTS was used. The kinetic characteristics of the system were determined independently for each significant system step. However, it proved difficult to simulate the coupled process completely with the kinetic data obtained independently, as true reaction conditions are not covered by kinetic experiments. A mixed approach using a system of ordinary differential equations corrected with data from the process (e.g. enzyme activity) leads to a satisfactory description. This model was applied as a starting point for identifying the relevant process parameters.

Continuous Homogeneous Asymmetric Transfer Hydrogenation of Ketones: Lessons from Kinetics

“…Furthermore, it is not always possible to account for continuous conditions by kinetic investigations 19. 21 Catalysts suitable for continuous operation are chosen for stability reasons rather than for short‐lived activity.…”

Membranes in Biotechnology

“…The cofactor NAD + was regenerated by anodic oxidation of NADH using ABTS (2,2¢-azinobis(3-ethyl-benzothiazolin-6-sulfonate) as the mediator [52]. Electrochemical oxidation, ultrafiltration, extraction and distillation were combined in one single system.…”

Specific Ion Effects on the Mediated Oxidation of NADH

“…The process utilises an enzymatic cofactor regeneration process catalysed by formate dehydrogenase . Cofactor regeneration based on enzymatic, electrochemical, chemical, and photochemical methods has been described, with enzymatic methods used most commonly . Enzymatic regeneration is widely used as it displays high selectivity and efficiency, however it requires the use of additional enzymes and substrates in order to regenerate the cofactor.…”

“…Kochius et al. [29] demonstrated that ABTS (2,2‐azino‐bis‐(3‐ethyl‐benzo‐thiazoline‐6‐sulfonic acid) is a highly efficient mediator for the regeneration of NADH with a high turnover factor (TF) of 1200 h −1 which compares very favourably with mediators such as methylene blue or methylene green (TF 75 h −1 and 25 h −1 respectively) . Moreover, ABTS can be easily used in large scale systems (i. e. reactors) because of its high stability in a broad range of conditions.…”

“…The mechanism of the reaction between NADH and ABTS occurs via the formation of a radical cation ABTS + . As proposed by Liese, the ABTS‐mediated mechanism of NADH regeneration involves the following steps [Eqs. (2)–]: …”