Resolution, classical biocatalytic

Comparison of Classical Resolution with the Biocatalytic Procedure... 

The practical advantages of the biocatalytic versus the classical procedure at large-scale consist of a) a reduced number of steps in the biocatalytic reaction (1 step) versus the classical organic resolution (5 steps), b) reduced production costs compared with the resolution with brucine, c) a reduced reactor volume of only 20%, d) improved environmental, health and safety conditions, because no toxic agent is involved, and e) expanded volume capacity, because no investment in additional equipment is necessary with a 5-fold scale-up. 

Attempts to resolve the racemic acid of 3 and its ester through classic resolution failed. In the early stages of development, a process based on SchoUkopf s asymmetric synthesis was developed (see Section 9.3). Large-scale development work was aimed at finding a biocatalytic process to resolve the amino acids. Racemic a,a-disubstituted a-amino esters were synthesized by standard chemistry through alkylation of the Schiff s bases formed from the amino esters (Scheme 9.5), or through formation of hydantoins. ... 

CHIRAL METHODOLOGIES USED IN MEDICINAL CHEMISTRY FOR DRUG DISCOVERY Classical resolution Biocatalytic resolution... 

In spite of these trends, cases in which novel biocatalytic resolutions (as opposed to utilization of established enzyme-substrate combinations) are reported as part of drug discovery programmes are relatively few compared with classical and other non-biological resolution techniques Schemes 5.7-5.11 show examples from the 1994 literature. 

In order to produce this desired stereoisomer, the employment of biocatalytic methods shows more advantages than the classical synthetic methods, due to the excellent yield and optical purity that can be reached using much milder experimental conditions. In this way, the kinetic resolution of racemic mixtures of APAs using lipases constitutes a preferable alternative versus the employment of whole cells because of ... 

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