Penicillin from Alcaligenes faecalis

A two-step approach, involving repeated use of the same enzyme, has been reported for the resolution of rac-l-phenylethylamine 56a (Scheme 2.34). Penicillin acylase, from Alcaligenes faecalis, was initially used in aqueous medium with (R)-phenylglycine amide 67 as the acyl donor. Under these conditions, the enzyme catalyzed the enantioselective acylation of 56a at pH 10-11. The product amide 68 was insoluble, and was collected and re-exposed to the enzyme at pH below 7.5. This resulted in the cleavage of the phenylglycinyl substituent. Excellent conversions, E values and enantiomeric excesses were achieved [36]. 

For example, we showed that penicillin acylase from Alcaligenes faecalis could be used for acylation of amines in an aqueous medium at high pH. After extraction of the remaining amine isomer, the pH was reduced to 7 and the amide hydrolyzed to afford the other amine enantiomer (Fig. 9.20). 

Amide formation and hydrolysis is of course also catalysed by enzymes and the recent report that the penicillin acylase from Alcaligenes faecalis catalyses an efficient kinetic resolution of racemic primary amines is very promising. A typical case is our old friend a-methylbenzylamine 57 (see chapter 22). One equivalent of an acyl donor 58 is needed and nearly 50% of the amide 59 can be isolated in excellent ee. The E value is 350 for this amine.20... 

Cheng S, Wei D, Song Q (2006) Extraction of penicillin G acylase from Alcaligenes faecalis in recombinant Escherichia coli with cetyl-trimethylammoniumbromide. Biochem Eng J 32(1)56-60... 

Nondynamic resolution processes for the production of chiral amines are based on selective N-acylation by either lipases from Burkholderia plantarii (Scheme 4.5C) or Alcaligenes faecalis penicillin G acylases (Scheme 4.5D). The former reaction is optimal with ethylmethoxyacetate as acylating agent [30 a], whereas fhe acylase is most selective with the natural substrate phenylacetic acid [30b]. 

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