Hydrolase-catalyzed continuous-flow

Hydrolases — especially lipases — proved to be versatile biocatalysts for synthetic biotransformations [79, 80). The vast majority of the enzymatic stereoselective processes have been performed so far in batch mode [29, 30, 81]. Very recently, a review appeared on lipase-catalyzed reactions under continuous-flow conditions [82], and here we extend this overview with an analysis of the range of selectivities, effects of reaction conditions and the mode of enzyme immobilization on the lipase, and in general hydrolase-catalyzed continuous-flow biotransformations. 

The hydrolase-catalyzed continuous-flow techniques were applied on laboratory scale for KRs of various amines (Figure 9.7 and Table 9.5). The lipase-catalyzed KR of racemic amines 19a-d with ethyl acetate and CaLB was performed in batch and continuous-flow PBR systems yielding (R)-amides (R)-20a-d in high enantiopurity... 

Stereoselective Hydrolase-Catalyzed Processes in Continuous-Flow Mode... 

Hydrolases, especially lipases are ideal to perform acylations such as direct esterification of free acids, acylation of alcohols, or amines in low-water organic media [29, 30, 60, 79, 81, 83]. Accordingly, the majority of the examples of hydrolase-catalyzed acylations in continuous-flow mode are enantiomer selective KRs (Figures 9.7-9.9 and Tables 9.5-9.6). Most of the earlier studies were aimed at the biocatalytic production of chiral pharmaceutical intermediates and were performed at a relatively large scale using immobilized lipases in PER [60, 99-102]. 

The most typical type of hydrolase-catalyzed stereoselective reactions under continuous-flow conditions is KR. Continuous-flow KRs were performed on racemic acids by direct esterification with alcohols [100-102, 108, 109] or on racemic amines by acylation with esters (Figure 9.7 and Table 9.5) [110-114]. However, the most frequent so far is the continuous-flow KR of racemic primary... 

Figure 9.8 Hydrolase-catalyzed kinetic resolution of primary alcohols 21a-c by acylation in continuous-flow PBR.

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