Monitoring the Progress of Lipase-Catalysed Resolutions

For both reactions, the opposite, and much faster, hydrolysis reaction can also be performed in order to resolve racemic esters. In this instance, the reaction is performed in water containing a small quantity of organic solvent (typically 10%) to aid dissolution of the substrate and products. 

The progress of any given lipase-catalysed reaction is monitored using two main indicators. The enantiomeric excess of either the starting material or product gives a measure of the enantioselectivity of the reaction. High enantioselectivity 

Equations 4.2 and 4.3 give rehable results except at very low and very high extents of conversion where accurate measurements are restricted by errors derived from sample manipulation. The use of Equation 4.4 is therefore preferred requiring the measurement of enantiomeric excess values only. E values less than 15 are unacceptable, between 15 and 30 are moderate to good and above 30 are excellent for use in organic synthesis, translating into an ee of 95%. 

An empirical rule was postulated by Jing and Kazlauskas to predict the enantiomer that reacts more quickly in a lipase-catalysed esterification reaction of a racemic secondary alcohol. The relative sizes of the two substituents determine the KR product [6]. X-ray structures of Upases revealed that the alcohol-binding pocket possesses a large hydrophobic pocket that is accessible to solvent along with a second, smaller pocket. The enantiopreference of lipases therefore allows for the determination of the absolute configuration of secondary alcohols. Clearly, the reliability of this method is dependent on how similar the molecule under study is to a molecule with a known absolute configuration in KR. The empirical rule to date only applies 

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