Biocatalysis classical reaction

Given the wide utility of biocatalysis in the fine chemical industry, why is there such an in-house reliance on classical methods of enantioseparation In fact, why is biocatalysis not applied more generally as a replacement for atom-inefficient or hazardous reactions that are intensively used in the pharmaceutical industry, such as amidation, reduction and oxidation ... 

An interesting alternative that combines the advantages of both classical and quantum mechanics is to use hybrid QM/MM models, first introduced by Arieh Warshel for modeling enzymatic reactions [7]. Here, the chemical species at the active site are treated using high-level (and therefore expensive) QM models, which are coupled to a force field that describes the reaction environment. Hybrid models can thus take into account solvent effects in homogeneous catalysis, support structure and interface effects in heterogeneous catalysis, and enzyme structure effects in biocatalysis. 

Biocatalysis has many advantages in the context of green chemistry, e.g. mild reaction conditions and often fewer steps than conventional chemical procedures because protection and deprotection of functional groups are often not required. Consequently, classical chemical procedures are increasingly being replaced by cleaner biocatalytic alternatives in the fine chemicals industry (see later). 

CCCs may obtain chiral compounds by classical resolution, kinetic resolution using chemical or enzymatic metlrods, biocatalysis (enzyme systems, whole cells, or cell isolates), fermentation (from growing whole microorganisms), and stereoselective chemistry (e.g., asymmetric reduction, low-temperature reactions, use of chiral auxiliaries). CCCs may also be CCEs by capitalizing on a key raw material position and going downstream. Along with companies manufacturing chiral molecules primarily for other purposes, such as amino acid producers, these will be the key sources for the asymmetric center. 

Substrate synthesis, reaction parameters, enantioenrichment via biocatalysis, catalyst handling, economic considerations Catalyst screening, substrate design, process optimization, application of Josiphos ligands, ligand synthesis, scale-up Production considerations, comparison with classical methods... 

Whereas biocatalysis previously was a last option that was only looked into when all other synthetic methods had failed, it is now a discipline well integrated into classical organic synthesis in the pharma-, agro-, and fine chemical industries [2]. An example from the latter group is laboratory chemicals producer Fluka, which has reported over 100 biocatalytic processes in routine production [3]. Biocatalysis can offer outstanding chemo-, regio- and/or enantioselectivities under mild reaction conditions. It is, hence, often used to create chirality, for example, in the pharma industry [4]. 

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