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Hall, M.; Faber, K.; Tasnádi, G., Science of Synthesis: Biocatalysis in Organic Synthesis, (2015) 1, 313.
As an alternative to acylase I, penicillin G acylase (PGA) can also be applied for the hydrolysis of N-acyl amino acids. Penicillin acylases (EC 3.5.1.11) cleave the acyl moiety of penicillins to yield 6-aminopenicillanic acid. Among them, penicillin G acylase, which hydrolyzes the phenylacetyl group from penicillin G, has been extensively studied[66] and used in the synthesis of semisynthetic penicillin antibiotics[67,68] and in peptide synthesis representing a mild protecting group manipulating tool,[20,69] as well as in various biocatalytic reactions.[70] As can be delineated from its natural substrate (PenG), penicillin G acylase is highly specific for phenylacetic acid, and only small groups, such as hydroxy or amino groups, are allowed at the 2-position of the acyl moiety, while the penicillin-recognizing subsite is highly specific for S-amino acids but also discriminates other chiral primary amines.[71] α-Amino acids are good substrates,[72–75] but, interestingly, a number of N-phenylacetyl β-amino acids[76–80] and esters,[81] and even γ-amino acids[82] have been resolved with penicillin G acylase. It seems that the carboxylic acid function is not essential for substrate acceptance; this has been demonstrated by the enantioselective hydrolysis of N-phenylacetyl aminophosphonic and aminophosphonous acids.[83,84] The enzyme is commercially available, also in an immobilized form. Scheme 7 shows examples of the enantioselective hydrolysis of N-phenylacetyl β-amino acids 13. It is important to mention that penicillin G acylase is highly S-selective toward α-amino acid derivatives, but is less faithful with β-analogues, as the priority of the substituents can occasionally change depending on the substitution pattern, leading to an apparent R selectivity.
Meeeee 8 Meeeeee Meeeeeeeee ee M-Meeeeeeeeeee β-Meeee Meeee eee Meeeee eeee Meeeeeeeee M Meeeeee[88,88,88]
M8 | M8 | M8 | Meeeeeeee Meeeeeeeee | Meeeeeeeeee (%) | Meeee Meee Meeeee 88M | Meeee Meee Meeeee 88M | Mee | ||
---|---|---|---|---|---|---|---|---|---|
eee (%) | Meeeee (%) | eee (%) | Meeeee (%) | ||||||
MM8 | M | M | 8M | 88e | >88 | 88 | >88 | 88 | [88] |
MM8MM8 | M | M | 8M | 88e | >88 | 88 | >88 | 88 | [88] |
(MM8)8MM8 | M | M | 8M | 88e | >88 | 88 | >88 | 88 | [88] |
MMM8 | M | M | 8M | 88e | >88 | 88 | >88 | 88 | [88] |
Me | Me | M | 8M,8M | 88 | >88 | e.e. | >88 | e.e. | [88] |
Me | Me | M | 8M,8M | 88 | >88 | e.e. | >88 | e.e. | [88] |
Me | MM8MM=MM8 | M | 8M,8M | 88 | 88 | e.e. | 88 | e.e. | [88] |
Me | Me | M | 8M,8M | 88 | >88 | e.e. | >88 | e.e. | [88] |
M≡MM | M | Me | 8M | e.e. | e.e.e | 88 | e.e.e | 88e | [88] |
M≡MMMM | M | Me | 8M | e.e. | e.e.e | 88 | e.e.e | 88e | [88] |
e e.e. = eee eeeeeeee.
e Mee eeeeeeee; eeeeeeeee eeee ee eeeeee.
e Mee eeeeeee eee eeeeeee ee ee eeeeeeeeeeeeeeee.
e Meeee (%) ee eeeeeeeee M-eeeee 88M.
Meeeeeeeeeee Meeeeeeee
Meeee (M)-8-Meeee-8-(eeeeeeeeeeeeee)eeee-8-eeeeee (88M, M8 = M≡MMMM; M8 = M; M8 = Me) eee Meeee (M)-8-(8-Meeeeeeeeeeeeee)-8-(eeeeeeeeeeeeee)eeee-8-eeeeee (88M, M8 = M≡MMMM; M8 = M; M8 = Me); Meeeeee Meeeeeeee:[88]
8.88 M Meeeeeeee eeeeee (eM 8.8; 888 eM) eee eeeee ee eeeeeee eeeee 8-(8-eeeeeeeeeeeeeee)-8-(eeeeeeeeeeeeee)eeee-8-eeeeee (88, M8 = M≡MMMM; M8 = M; M8 = Me; 8 e, 88 eeee). Meeeeeeeeee eeeeeeeeee M eeeeeee (8 e, 888 M · e−8; eeeeeeee eeee Meeeeeeeee Meeeeeee) eee eeeee. Mee eeeeeee eee eeeeeee ee ee. Mee eM ee eee eeeeee eee eeee ee eeeee 8.8 eeeee eee MMMM8 eeee (eee. MMMM8/M8M 8:8) eeee ee eeeeeeeeeeee. Meeee eeeee eeeeeee eee 88 e, eee eeeeeee eee eeeeeeeee eeee MeMMe (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeeee eee eeeeeeeee eeee eee MMe (eM 8; 8 × 88 eM). Mee MMe eeeeeeee eeee eeeeeeee eee eeeeeeeee. Mee eeeeeee eeeeeee eee eeeeee eeee eee MMMM8 (eM 8; 8 × 88 eM), eeeee (Me8MM8), eee eeeeeeeeeeee ee eeeeeee eeeee eeeeeee eeeeeeee ee eeeeee eeeeeeeee M-eeeee 88M (M8 = M≡MMMM; M8 = M; M8 = Me) ee e eeeee eeeeeeeeeee eeeeeeee; eeeee: 8.8 e (88%).
Mee eeeeee eeeeeee eeeee eeeeeeeeee eee eeeee eee eeeeeeee eeeee eee MMMM8 ee eeeeee eM ~8.8 eee eeeeeeeee eeee MeMMe (8 × 88 eM). Mee MeMMe eeeeeeee eeee eeeeeeee, eeeee (Me8MM8), eee eeeeeeeeeeee ee eeeeeee eeeee eeeeeee eeeeeeee ee eeeeee M-eeeee 88M (M8 = M≡MMMM; M8 = M; M8 = Me); eeeee: 8.88 e (88%).
References
[20] | Meeeeeee, M.; Meeeeeee, M., Meee. Mee., (8888) 888, 8888. |
[66] | Meeeee, M.; ee ee Meee, M.; Meeeee, M.; Meeee Meeeeeeóe, M., Meee. Meeeeeeee. Meeeeeeeee., (8888) 88, 888. |
[67] | Meeeeee, M.; Meeeeeeee, M. M.; Meeeeeeee-Meeeeeee, M., Meee. Mee. Meee., (8888) 88, 8888. |
[68] | Meeeeeeee, M.; Mee, M.; Meeee, M.; Meeeeeeee, M.; Mee-Meeee, M.; Meee, M. M., Meeeeeeeee. Mee., (8888) 88, 8888. |
[69] | Meeeee, M.; Meeeeeee, M., Meee. Meee. Meee. Meee., (8888) 8, 888. |
[70] | Meeeeee, M.; Šeěeáeee, M.; Meeeíe, M., Meeeeeeeee. Mee., (8888) 88, 8888. |
[71] | Šeeeee, M. M.; Meeeeeeee, M. M.; Meeeeee, M. M.; Meeeeee, M. M., Mee. M. M. Meee. Mee., (8888) 888, 888. |
[72] | Meeeeeee, M. M.; Meeeeeeeee, M.; Meeeeee, M. M.; Meeeeeee, M. M., M. Meee. Mee., Meeeee Meeee. 8, (8888), 8888. |
[73] | Mee, M. M.; Meee, M. M.; Mee, M. M.; Meeee, M. M.; Meee, M. M., Meee. Meeeeee. Meeeeeeeee., (8888) 88, 888. |
[74] | Meeeeeee, M. M.; Meee, M. M.; Meeee, M. M., Meeeeeeeeee: Meeeeeeee, (8888) 88, 8888. |
[75] | Meeeeeeeee, M.; Meeeeeeeee, M.; Meeee, M. M.; Meeeeeee, M. M., Meeeeeeeeee: Meeeeeeee, (8888) 88, 8888. |
[76] | Meeeeeeeee, M. M.; Meeeeeeee, M. M.; Meeeee, M. M.; Meeeeeeee, M. M.; Meeeeeee, M. M.; Meeeee, M. M.; Šeeeee, M. M.; Meeeeee, M. M., Meeeeeeeeee: Meeeeeeee, (8888) 8, 8888. |
[77] | Meeeeeeeee, M. M.; Meeeeeeee, M. M.; Meeeee, M. M.; Meeeee, M. M.; Meeeeeee, M. M.; Šeeeee, M. M.; Meeeeee, M., Meeeeeeeeee: Meeeeeeee, (8888) 8, 8888. |
[78] | Meeeeeee, M.; Meeeeeeee, M.; Meeeeeee, M., M. Mee. Meee., (8888) 88, 8888. |
[79] | Meeeeeeeee, M. M.; Meeeee, M. M.; Meeeee, M. M.; Meeeeeeee, M. M.; Meeeeeee, M. M.; Meeeeeeee, M. M.; Meeeee, M. M.; Meeee, M. M.; Meeeee, M. M.; Meeeeee, M. M.; Meeeeeeee, M. M.; Meeeeeee, M. M., Meeeeee, (8888), 888. |
[80] | Meeeeeee, M.; Meeeeeeeee, M.; Meeeeeeee, M.; Meeeeeee, M., M. Mee. Meee., (8888) 88, 8888. |
[81] | Meeee, M. M.; Me, M. M.; Meeeee, M.; Meee, M.; Meeeeee, M. M., Meeeee. Mee. Meee., (8888) 8, 8888. |
[82] | Meeeeeee, M. M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[83] | Meeeeeeee, M. M.; Meeeeee, M. M.; Meeeee, M. M.; Meeeeee, M. M.; Meeeeeeee, M. M.; Šeeeee, M. M., Meeeeeeeeee, (8888) 88, 8888. |
[84] | Meeeeeeee, M. M.; Meeee, M. M.; Meeeeeee, M. M.; Meeeee, M. M.; Meeeeee, M. M.; Meeeeeeee, M. M.; Meeeee, M. M., Meeeeeeeeee: Meeeeeeee, (8888) 8, 8888. |