Process for preparing optically active indoline-2-carboxylic acid

• US 4,898,822 A
• Filed: 03/31/1986
• Issued: 02/06/1990
• Est. Priority Date: 04/01/1985
• Status: Expired due to Fees

• Current Assignee: Kanegafuchi Kagaku Kogyo Kabushiki Kaisha
• Original Assignee: Kanegafuchi Kagaku Kogyo Kabushiki Kaisha
• Inventors: Asada, Masanori, Hamaguchi, Shigeki, Katsuki, Hidetoshi, Takahara, Kenji, Watanabe, Kiyoshi, Takahashi, Hideyuki, Nakamura, Yoshio, Ohashi, Takehisa, Shimada, Yoshio
• Primary Examiner(s): Warren, Charles F.
• Assistant Examiner(s): Marx, Irene
• Application Number:
  US06/846,436
• Time in Patent Office: 1,408 Days
• Field of Search: 435/180, 435/280, 435/220, 435/223, 435/224, 435/225, 435/197, 435/198, 435/135, 435/136, 435/117, 435/118, 435/119, 435/822, 435/120, 435/121
• US Class Current: 435/121
• CPC Class Codes: C12P 17/10 Nitrogen as only ring hetero atom
• CPC Class Codes: C12P 41/005 by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
• CPC Class Codes: Y10S 435/83 Arthrobacter
• CPC Class Codes: Y10S 435/839 Bacillus subtilis
• CPC Class Codes: Y10S 435/843 Corynebacterium
• CPC Class Codes: Y10S 435/874 Pseudomonas
• CPC Class Codes: Y10S 435/897 Streptomyces griseus
• CPC Class Codes: Y10S 435/911 using fungi
• CPC Class Codes: Y10S 435/921 Candida
• CPC Class Codes: Y10S 435/925 Cephalosporium

Abstract

A process for preparing optically active indoline-2-carboxylic acid by an optical resolution, which comprises subjecting a racemic ester of (R,S)-indoline-2-carboxylic acid having the general formula [(R,S)-I] to the action of an enzyme or a microorganism having a stereo-selective esterase activity, which is capable of asymmetrically hydrolyzing the racemic ester [(R,S)-I] to give optically active indoline-2-carboxylic acid having the formula [II*] so as to produce the hydrolysis product, i.e. optically active indoline-2-carboxylic acid [II*] and an unreacted optically active ester of indoline-2-carboxylic acid having the general formula [I*], isolating each optically active form, and further, if necessary, hydrolyzing the obtained optically active ester [I*] to give an optical antipode of the acid [II*].

According to the process of the present invention, optically active indoline-2-carboxylic acid with a high optical purity can be prepared in a simple process with a good yield.

Claims

1. A process for preparing an (R)-indoline-2-carboxylic acid having the formula [(R)-II]:

##STR12## which comprises subjecting a racemic ester of an (R,S)-indoline-2-carboxylic acid having the formula [(R,S)-I)];

##STR13## wherein R is an alkyl or alkenyl group having 1 to 10 carbon atoms;

an alkyl or alkenyl group having 1 to 10 carbon atoms substituted with either hydroxyl group or a halogen atom, or simultaneously substituted with both hydroxyl group and a halogen atom;

or a substituted or unsubstituted aromatic hydrocarbon group, to the action of an enzyme selected from the group consisting of Protease Amano P, Bioplase AL 15, Actinase E, Pancreatic digesting enzyme TA, Steapsin and Lipase L 3216, or a microorganism selected from the group consisting of Aspergillus melleus IFO 4420, Bacillus subtilis IFO 3018, Streptomyces griseus IFO 8358, Saccharomyces cerevisiae HUT 7018, Trichosporon cutaneum IFO 1200, Aeromonas hydrophila IFO 3820, Arthrobacter paraffineus ATCC 21317, Arthrobacter nicotianae IFO 14234, Acidiphilium cryptum IFO 14242, Brevibacterium protophormiae IFO 12128, Corynebacterium paurometabolum IFO 12160 and Pseudomonas oxalacticus IFO 13593, or a stereoselective esterase from any of these microorganisms, to asymmetrically hydrolyze the racemic ester [(R,S)-I] into optically active (R)-indoline-2-carboxylic acid [(R)-II] and an ester of (S-indoline-2-carboxylic acid having the formula [(S)-1] ##STR14## wherein R is as above, and then isolating the optically active (R)-indoline-2-carboxylic acid [(R)-II].

2. The process of claim 1, wherein said racemic ester of (R, S)-indoline-2-carboxylic acid [(R,S)-I] is subject to the action of said enzyme or microorganism immobilized on a hydrophobic support.

7. The process of claims 2, 4, 5 or 6, wherein said hydrophobic support for immobilizing the enzyme or microorganism is a member selected from the group consisting of a synthetic adsorbent, a hydrophobic resin for chromatography, a hydrophobic photo induced crosslinked-resin and a macromolecule material in which a hydrophobic group is introduced by a chemical bonding.

8. The process of claim 2, 4, 5 or 6, wherein said asymmetric hydrolysis is carried out with said immobilized enzyme or microorganism filled in a column.

9. The process of claim 2, 4, 5 or 6, wherein said asymmetric hydrolysis is carried out in a batch process.

3. A process for preparing an (S)-indoline-2-carboxylic acid having the formula [(S)-II]:

##STR15## which comprises subjecting a racemic ester of an (R,S)-indoline-2-carboxylic acid having the formula [(R,S)-I];

##STR16## wherein R is an alkyl or alkenyl group having 1 to 10 carbon atoms;

an alkyl or alkenyl group having 1 to 10 carbon atoms substituted with either hydroxyl group or a halogen atom, or simultaneously substituted with both hydroxyl group and a halogen atom, or a substituted or unsubstituted aromatic hydrocarbon group, to the action of an enzyme selected from the group consisting of Lipoprotein lipase and Lipase AP 6, or a microorganism selected from the group consisting of Pseudomonas aeruginosa IFO 3080, Aspergillus niger IFO 4407, Arthrinium phaeospermum IFO 5703, Aspergillus ficuum IFO 4280, Cephalosporium mycophilum IFO 8580, Echinopodospora jamaicensis IFO 30406, Emericellopsis glabra IFO 9031, Hypocrea lactea IFO 8434, Isaria atypicola IFO 9205, Lepista nuda IFO 8104, Nectria flammea IFO 30306, Pestalotiopsis distincta IFO 9981, Phialophora fastigiasta IFO 6850, Podospora carbonaria IFO 30924, Botryoascus synnaedendrus IFO 1604, Candida diversa IFO 1090, Citeromyces matritensis IFO 0651, Debaryomyces hansenii IFO 0015, Hormoascus platypodis IFO 1471, Moniliella tomentosa CBS 22032, Kluyveromyces fragilis IFO 0288, Nadsonia elongata IFO 0665, Rhodotorula glutinis IAM 4642, Schizosaccharomyces pombe IFO 0347, Torulopsis gropengiesseri IFO 0659, Wickerhamia fluorescens IFO 1116, Alcaligenes faecalis IFO 12669, Arthrobacter crystallopoietes IFO 14235, Brevibacterium flavum ATCC 21269, Protaminobacter alboflavus IFO 3707 and Pseudomonas acidovorans IFO 13582, or a stereoselective esterase from any of these microorganisms, to asymmetric hydrolyze the racemic ester [(R,S)-I] into optically active (S)-indoline-2-carboxylic acid [(S)-II] and an ester of (R)-indoline-2-carboxylic acid having the formula [(R)-I];

##STR17## wherein R is as above, and then isolating the optically active (S)-indoline-2-carboxylic acid [(S)-II].

4. The process of claim 3, wherein said racemic ester of (R,S)-indoline-2-carboxylic acid [(R,S)-I] is subjected to the action of said enzyme or microorganism immobilized on a hydrophobic support.

5. A process for preparing an (R)-indoline-2-carboxylic acid having the formula [(R)-II]:

##STR18## and an (S)-indoline-2-carboxylic acid having the formula [(S)-II];

##STR19## which comprises;

(a) contacting a racemic ester of (R,S)-indoline-2-carboxylic acid having the formula [(R,S)-I];

##STR20## wherein R is an alkyl or alkenyl group having 1 to 10 carbon atoms;

an alkyl or alkenyl group having 1 to 10 carbon atoms substituted with either hydroxyl group or halogen atom, or simultaneously substituted with both hydroxyl group and a halogen atom;

or a substituted or unsubstituted aromatic hydrocarbon group, with an enzyme selected from the group consisting of Protease Amano P, Bioplase AL 15, Actinase E, Pancreatic digesting enzyme TA, Steapsin and Lipase L 3216, or a microorganism selected from the group consisting of Aspergillus melleus IFO 4420, Bacillus subtilis IFO 3018, Streptomyces griseus IFO 8358, Saccharomyces cerevisiae HUT 7018, Trichosporon cutaneum IFO 1200, Aeromonas hydrophila IFO 3820, Arthrobacter paraffineus ATCC 21317, Arthrobacter nicotianae IFO 14234, Acidiphilium cryptum IFO 14242, Brevibacterium protophormaiae IFO 12128, Corynebacterium paurometabolum IFO 12160 and Pseudomonas oxalacticus IFO 12160, or a stereoselective esterase from any of thee microorganisms, immobilized on a hydrophobic support to asymmetrically hydrolyze said racemic ester [(R,S)-I] into optically active hydrophilic (R)-indoline-2-carboxylic acid [(R)-II] and an ester of (S)-indoline-2-carboxylic acid having the general formula [(S)-I] ##STR21## wherein R is as above, (b) eluting the (R)-indoline-2-carboxylic acid [(R)-II], and

(c) hydrolyzing the ester of (S)-indoline-2-carboxylic acid [(S)-I] with an alkali to form (S)-indoline-2-carboxylic acid [(S)-II] and eluting the thus formed (S)-indoline-2-carboxylic acid [(S)-II].

6. A process for preparing an (R)-indoline-2-carboxylic acid having the formula [(R)-II]:

##STR22## and an (S)-indoline-2-carboxylic acid having the formula [(S)-II];

##STR23## which comprises (a) contacting a racemic ester of (R,S)-indoline-2-carboxylic acid having the formula [(R,S)-I];

##STR24## wherein R is an alkyl or alkenyl group having 1 to 10 carbon atoms;

an alkyl or alkenyl group having 1 to 1 carbon atoms substituted with either hydroxyl group or a halogen atom, or simultaneously substituted or unsubstituted aromatic hydrocarbon group, with an enzyme selected from the group consisting of Lipoprotein lipase and Lipase AP 6, or a microorganism selected from the group consisting of Pseudomonas aeruginosa IFO 3080, Aspergillus niger IFO 4407, Arthrinium phaeospermum IFO 5703, Aspergillus ficuum IFO 4280, Cephalosporium mycophilum IFO 8580, Echinopodospora jamaicensis IFO 30406, Emericellopsis glabra IFO 9031, Hypocrea lactea IPO 8434, Isaria atypicola IFO 9205, Lepista nuda IFO 8104, Nectria flammea IFO 30306, Pestalotiopsis distincta IFO 9981, Phialophora fastigiasta IFO 6850, Podospora carbonaria IFO 30294, Botryoascus synnaedendrus IFO 1604, Candida diversa IFO 1090, Citeromyces matritensis IFO 0651, Debaryomyces hansenii IFO 0015, Hormoascus platypodis IFO 1471, Moniliella tomentosa CBS 22032, Kluyveromyces fragilis IFO 0288, Nadsonia elongata IFO 0665, Rhodotorula glutinis IAM 4642, Schizosaccharomyces pombe IFO 0347, Torulopsis gropengiesseri IFO 0659, Wikerhamia fluorenscens IFO 1116, Alcaligenes faecalis IFO 12669, Arthrobacter crystallopoietes IFO 14235, Brevibacterium flavum 21269, Protaminobacter alboflavus IFO 3707 and Pseudomonas acidovorans IFO 13582, or a stereoselective esterase from any of these microorganisms, immobilized on a hydrophobic support to asymmetrically hydrolyze said racemic ester [(R,S)-I] into optically active hydrophilic (S)-indoline-2-carboxylic acid [(S)-II] and an ester of (R)-indoline-2-carboxylic acid having the general formula [(R)-I];

##STR25## wherein R is as above, (b) eluting hydrophilic (S)-indoline-2-carboxylic acid [(S)-II],

(c) hydrolyzing said ester of (R)-indoline-2-carboxylic acid [(R)-I] with an alkali to form (R)-indoline-2-carboxylic acid [(R)-II] and eluting the thus formed (R)-indoline-2-carboxylic acid [(R)-II].