Practical lipase-catalyzed esterification reaction

Practical Exercise Lipase-Catalyzed Esterification Reaction [62]... 

In the past decade or so, lipase-catalyzed esterifications and transesterifications in anhydrous media (e.g., organic solvents and supercritical fluids) have been an area of intensive research. In particular, the use of organic solvents, which normally allow a higher stability of enzymes than in water (Bock, Jimoh, Wozny, 1997), has been demonstrated. Reviews of the applications have been made by Hail Krishna and Karanth (2002) and Gandhi et al. (2000), dealing with fundamental and practical aspects of lipase catalysis. In particular, they concentrated on various immobilization strategies and factors (e.g., temperature, reaction medium, water activity) as weU as the methods of preparation (which affect and influence the stability of the lipases). 

If reactants A and B, and product C, are fluids, then continuous flow, solvent-free conditions may be suitable. This does, however, pose practical problems of efficient mixing between A and B, which can be made more difficult if either is viscous, or the reactions are fast. Within the polymer and food industries there are examples of both continuous solid and melt extrusion processes, though few involve reactive chemistiy. If the reaction is selective then product C can be isolated directly, otherwise its higher molecular weight may make it difficult to separate without using a solvent, negating the aim, unless it is a solid. An example of a solvent-free continuous flow process is the lipase-catalyzed esterification of fatly esters using alcohols, as shown in Scheme 12.1. ... 

Biocatalysis is normally performed in an aqueous environment, but can in many cases also be conducted in solvent mixtures, liquid-liquid two-phase systems, and even in pure organic solvents. This extends the traditional (natural) application range of biocatalysis to more lipophilic starting materials and opens up the way to new reactions. A relevant practical example is the use of esterases and lipases to catalyze esterifications in organic solvents such as vinyl acetate. 

Pharmacia Upjohn developed a practical synthesis toward the anticancer agent Irinotecan (Camptosar, 24), which involved an enzymatic resolution step to provide the strategic intermediate 23 (Scheme 7) [65,66]. Lactone 23 could be produced by internal esterification of oxidized (S)-diol 21, which in turn was obtained by biocatalytic resolution of mc-21. An asymmetric acetylation was achieved with isopropenyl acetate catalyzed by Amano PS-30 Pseudomonas cepacia) lipase immobilized on Celite and could be driven to 60% conversion. (S)-21 was isolated in 38% yield and with 99% optical purity, whereas the unwanted (i )-stereoisomer 22 was recycled in a three-step procedure. Changing the support to Celite 521 significantly increased the reaction rate, as did rais-... 

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