Racemic continuous flow system

Scheme 4.113 Continuous flow system for racemic resolution of amino acids. Reprinted with permission from [436], Copyright 2007 The Royal Society of Chemistry.

Figure 12.7 Continuous flow system for enantioselective separation of racemic amino acids. Reproduced by permission of the Royal Society of Chemist [26].

Numerous hydrolaseotalyzed KRs of various secondary alcohols were performed in continuous-flow mode (Figure 9.8 and Table 9.6). The bioimprinting effect in sol-gel immobilization of various lipases (Lipase AK, Lipase PS, CaLB, and CrL) was studied (116]. The performance of the immobilized biocatalysts were characterized by enantiomer selective acylation of various racemic secondary alcohols in two different multisubstrate systems (mix A rac-23a,c-e and mix B rac-23b and roc-23i) in batch and continuous-flow mode. The synthetic usefiilness of the best biocatalysts was demonstrated by the KR of racemic l-(thiophen-2-yl)ethanol (rac-23j) in batch and continuous-flow systems [116]. 

Figure 10.28 Continuous flow system for enantioselective separation of racemic amino acids. First, an L-body in the racemic substrate (4 mM) is enantioselectively converted into an amino acid through the tubing acylase-reactor. The pH of the resultant substrate solution is then lowered by addition of 0.2 M HCI that is...

In order to increase the efficiency of biocatalytic transformations conducted under continuous flow conditions, Honda et al. (2006, 2007) reported an integrated microfluidic system, consisting of an immobilized enzymatic microreactor and an in-line liquid-liquid extraction device, capable of achieving the optical resolution of racemic amino acids under continuous flow whilst enabling efficient recycle of the enzyme. As Scheme 42 illustrates, the first step of the optical resolution was an enzyme-catalyzed enantioselective hydrolysis of a racemic mixture of acetyl-D,L-phenylalanine to afford L-phenylalanine 157 (99.2-99.9% ee) and unreacted acetyl-D-phenylalanine 158. Acidification of the reaction products, prior to the addition of EtOAc, enabled efficient continuous extraction of L-phenylalanine 157 into the aqueous stream, whilst acetyl-D-phenylalanine 158 remained in the organic fraction (84—92% efficiency). Employing the optimal reaction conditions of 0.5 gl min 1 for the enzymatic reaction and 2.0 gl min-1 for the liquid-liquid extraction, the authors were able to resolve 240 nmol h-1 of the racemate. 

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... 

---