Biocatalytic asymmetric Michael addition reaction ofl-arginine to fumarate for the green synthesis of N-(([(4S)-4-amino-4-carboxy-butyl]amino)iminomethyl)-l-aspartic acid lithium salt (l-argininosuccinic acid lithium salt)

Abstract

The biocatalytic asymmetric Michael addition ofl-arginine to fumarate using argininosuccinate lyase (ASL) has enabled the synthesis of the key metabolitel-argininosuccinic acid lithium salt1for the first time, with excellent yield and purity.

Unraveling the Cyclization of l-Argininosuccinic Acid in Biological Samples: A Study via Mass Spectrometry and NMR Spectroscopy

“…Further analyses of the 13 C NMR of the equilibrium mixture at t = 12 h are shown in Figure S4. The detailed assignment of all the signals of ASA observed was done based on the 13 C NMR spectrum of ASA in water solution reported in previous studies. , All 13 C NMR signals for cyclic form 1 can be separated into different classes of carbon atoms using the editing technique DEPT, and according to their chemical shifts, most signals in this study were assigned to 1 . Thus, 13 C NMR displays five carbon signals, including four sp 3 methylenes (C-2, C-6, C-7, and C-9) and one sp 3 methine (C-9), and five sp 2 quaternary carbons (Figure S5).…”

Complexity reduction and opportunities in the design, integration and intensification of biocatalytic processes for metabolite synthesis

“…The analysis of chemical and biological routes for the synthesis of metabolites often shows large differences in the number of reaction steps required to construct highly and differentially functionalized small molecules. Designing highly selective and straightforward biocatalytic one-step synthesis methods instead of lengthy and challenging chemical routes has been established as the preferred method for preparative access to a large number of valuable metabolites (Richter et al, 2009;Schell et al, 2009;Matsumi et al, 2014;Schoenenberger et al, 2017a;Hardt et al, 2017;Schoenenberger et al, 2018;Krevet et al, 2020;Schoenenberger et al, 2020;Sun et al, 2021). As the finding and selection of routes is a key task in target-oriented synthesis the development of appropriate methodologies has attracted much interest in both chemistry and biology.…”

“…The relevant aspects of molecular economy for step integration include the optimization of the step economy by reducing the number of reaction steps, by more direct transformations or by eliminating protection-deprotection schemes, by avoiding intermediate isolation and downstream processing steps through coupling several reaction steps in one pot. The examples of the manufacturing processes for mevalonate 5-phosphate (Matsumi et al, 2014), shikimate-3phosphate (Schoenenberger et al, 2018), tagatose-1,6diphosphate (Schoenenberger et al, 2020), 2-keto-3-deoxy-D-gluconate (Matsubara et al, 2014) and L-argininosuccinate (Schoenenberger et al, 2017a) demonstrate the importance of complexity reduction. This can be achieved by reducing the number of steps, avoiding protecting groups, selective biocatalytic phosphorylation reactions, selective defunctionalization and simple addition reactions reducing complex chemical multi-step routes.…”

Biocatalysis in the Swiss Manufacturing Environment

“…The further extension of ketoreductase-catalyzed reductions of ketones has been first choice in manufacturing the chiral metabolites (R)-and (S)-lactaldehyde [53]. An argininosuccinate lyase-catalyzed Aza-Michael addition reaction of L-arginine to fumarate has been successfully used for building the molecule L-argininosuccinate in one step from simple starting materials [54].…”