Sequential lipase-catalyzed resolution

Scheme 18 Sequential lipase-catalyzed resolution of f/ireo-2,4-pentanediol by esterification [145]. The fast-reacting enantiomer is shown.

A sequential approach with a combined alcoholysis-esterification reaction has been used for the porcine pancreatic lipase-catalyzed resolution of 2-phenyl-l-propanol [148] (Scheme 20). The alcoholysis reaction (A) was run to 48% conversion followed by the addition of 3 equivalents of vinyl acetate. By this, 2-phenyl-l-propanyl acetate with 92% e.e. and in 20% yield was isolated. 

An additional strategy employed by Sih and co-workers involved sequential enzyme-catalyzed reactions. Pseudomonas lipases were found to tolerate a wide range of substrates although the enantioselectivity was generally only moderate. However, by first performing a methanolysis of the oxazolinone followed by a separate enzyme-catalyzed hydrolysis under kinetic resolution conditions, a highly enantio-merically enriched product could be obtained, as shown in Fig. 9-211491. 

Acyl-enzyme complexes are crucial intermediates in all lipase catalyzed reactions and thus the lipases first form an acyl-enzyme complex with the acyl donor. Eq. (8.75) displays a sequential two-step mechanism for enzymatic kinetic resolution of J4-l-phenyl ethyl alcohol to i4-l-phenyl ethyl acetate (route N ). 

In the aqueous phase enzymatic hydrolysis of racemic IPGA leads to IGP (mainly one enantiomer), which can be extracted into the supercritical fluid. Buffering of the pH in the aqueous solution is necessary to provide optimal conditions for the enzyme. In the following lipase-catalyzed esterification IPG reacts with vinyl but) to IPG-butyrate (lipase was from P. cepacia). In this sequential resolution of racemates no processing of intermediates is necessary both reactions take place in different phases (Fig. 19). 

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