There's No Industrial Biocatalyst Like Hydrolase: Development of Scalable Enantioselective Processes Using Hydrolytic Enzymes1
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- 作者：Yasuo Chikusa ; Yoshihiro Hirayama ; Masaya Ikunaka ; Toru Inoue ; Shunji Kamiyama ; Masafumi Moriwaki ; Yukifumi Nishimoto ; Fumiki Nomoto ; Kazuo Ogawa ; Tomoyasu Ohno ; Koutaro Otsuka ; Akiko K. Sakota ; Naoki
- 刊名：Organic Process Research & Development
- 出版年：2003
- 出版时间：May 2003
- 年：2003
- 卷：7
- 期：3
- 页码：289 - 296
- 全文大小：168K
- 年卷期：v.7,no.3(May 2003)
- ISSN：1520-586X
文摘
Chiral, racemic esters, ethyl (±)-tetrahydrofuran-2-carboxylate4c, methyl (±)-
-phenylpropionate 9b, methyl (±)-5,5-dimethyl-1,3-thiazolidine-4-carboxylate 12a, 2-methoxyethyl (±)-1-(4-tert-butylphenyl)-2-oxopyrrolidine-4-carboxylate 15a, (±)-1-benzyloxy-3-chloropropan-2-yl hydrogen succinate 18c, and (±)-3-butyryloxyquinuclidinium butyrate [(±)-20b·n-PrCO2H], areresolved kinetically by enantioselective hydrolysis catalyzed byan Aspergillus melleus protease [E = 60; 93.9% ee and 35%yield for (R)-tetrahydrofuran-2-carboxylic acid 4a], a Klebsiellaoxytoca hydrolase [E > 200; 99.5% ee and 36% yield for (S)--phenylpropionic acid 9a], a K. oxytoca hydrolase [E = 145;97.7% ee and 34% yield for (R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid 12b], a Bacillus brevis protease [E = 77; 99%ee and 45% yield for (S)-15a], a Serratia marcescence esterase[E = 49; 99% ee and 43% yield for (S)-18c], and an A. melleusprotease [E = 96; 96% ee and 42% yield for (R)-20b], respectively. Each enzymatic process is discussed with focus on thefollowing tactical issues: (1) identification of a hydrolase withhigh enantioselectivity, (2) substrate concentrations not less than1 M that allow for industrially viable volume efficiency (space-time yield), (3) product separation by partition between organicand aqueous phases, and (4) alleviation of a hydrolysateinhibiting the enzymatic activity.
-phenylpropionate 9b, methyl (±)-5,5-dimethyl-1,3-thiazolidine-4-carboxylate 12a, 2-methoxyethyl (±)-1-(4-tert-butylphenyl)-2-oxopyrrolidine-4-carboxylate 15a, (±)-1-benzyloxy-3-chloropropan-2-yl hydrogen succinate 18c, and (±)-3-butyryloxyquinuclidinium butyrate [(±)-20b·n-PrCO2H], areresolved kinetically by enantioselective hydrolysis catalyzed byan Aspergillus melleus protease [E = 60; 93.9% ee and 35%yield for (R)-tetrahydrofuran-2-carboxylic acid 4a], a Klebsiellaoxytoca hydrolase [E > 200; 99.5% ee and 36% yield for (S)--phenylpropionic acid 9a], a K. oxytoca hydrolase [E = 145;97.7% ee and 34% yield for (R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid 12b], a Bacillus brevis protease [E = 77; 99%ee and 45% yield for (S)-15a], a Serratia marcescence esterase[E = 49; 99% ee and 43% yield for (S)-18c], and an A. melleusprotease [E = 96; 96% ee and 42% yield for (R)-20b], respectively. Each enzymatic process is discussed with focus on thefollowing tactical issues: (1) identification of a hydrolase withhigh enantioselectivity, (2) substrate concentrations not less than1 M that allow for industrially viable volume efficiency (space-time yield), (3) product separation by partition between organicand aqueous phases, and (4) alleviation of a hydrolysateinhibiting the enzymatic activity.