Enantioselective synthesis of phenylacetamides in the presence of high organic cosolvent concentrations catalyzed by stabilized penicillin G acylase. Effect of the acyl donor.
Immobilization of penicillin G acylase on glyoxyl agarose and its further hydrophilization by physicochemical modification with ionic polymers has made it possible to perform the direct condensation between (+/-)-2-hydroxy-2-phenylethylamine [(+/-)-1] and different acyl donors in the presence of high concentrations of organic cosolvent (up to 90%) in the reaction medium. Using 50 mM phenyl acetic acid and these drastic reaction conditions, too harsh for any other PGA preparation, we have achieved an almost quantitative transformation (more than 99%) of 10 mM (+/-)-1 into the corresponding amide. Remarkably, the enantioselectivity of the enzyme immobilized on the amine was strongly dependent on the acyl donor employed. Thus, using phenylacetic acid (2), the enantioselectivity was almost negligible (1.3 favoring the S isomer), whereas using S-mandelic acid [(S)-4], the E factor reached a value of 21 (also favoring the S isomer). By using R-mandelic acid [(R)-4], we observed a different enantioselectivity (E was 3.6 favoring the R). At 4 degrees C, the E value reached a value higher than 100 when (S)-4 was used as the acyl donor. The reaction performed under these conditions allowed us to produce (2S,2'S)-N-2'-hydroxy-2'-phenyl)-2-hydroxyphenylacetamide [(2S,2'S)-7] with a diasteromeric excess higher than 98%.
Abian
Olga
O
Departamento de Biocatalisis, Instituto de Catalisis (CSIC), Campus UAM Cantoblanco, 28049 Madrid, Spain.
Mateo
César
C
Palomo
José M
JM
Fernández-Lorente
Gloria
G
Guisán
José M
JM
Fernández-Lafuente
Roberto
R
D000081:Acetamides / Q000737:chemistry*; D000215:Acylation; D004789:Enzyme Activation; D004795:Enzyme Stability; D004800:Enzymes, Immobilized / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D009930:Organic Chemicals / Q000737:chemistry*; D010084:Oxidation-Reduction; D010399:Penicillin Amidase / Q000737:chemistry*; D010627:Phenethylamines / Q000138:chemical synthesis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D000081:Acetamides; D004800:Enzymes, Immobilized; D009930:Organic Chemicals; D010627:Phenethylamines; D012997:Solvents; D010399:Penicillin Amidase