Process for producing carboxylic acid esters using carboxyesterase and an anhydride in organic solvent

• US 5,156,962 A
• Filed: 05/22/1990
• Issued: 10/20/1992
• Est. Priority Date: 11/28/1986
• Status: Expired due to Fees

• Current Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Kikumoto, Fumio, Suzuki, Takashi, Ohta, Kazuhiko
• Primary Examiner(s): Naff, David M.
• Assistant Examiner(s): SAUCIER, SANDRA E
• Application Number:
  US07/526,761
• Time in Patent Office: 882 Days
• Field of Search: 435/135, 435/133, 435/280, 435/76, 435/71.3
• US Class Current: 435/135
• CPC Class Codes: C12P 17/18 containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin e.g. Rifamycin C12P17/189
• CPC Class Codes: C12P 19/62 the hetero ring having eight or more ring members and only oxygen as ring hetero atoms, e.g. erythromycin, spiramycin, nystatin
• CPC Class Codes: C12P 7/62 Carboxylic acid esters

Abstract

A process for producing a carboxylic acid ester which comprises reacting a hydroxy compound for example a primary or secondary alcohol, lankacidin C or maridomycin with a carboxylic anhydride in the presence of carboxylesterase as a catalyst in an organic solvent.

Claims

1. A process for producing a carboxylic acid ester which comprises reacting an hydroxy group containing compound, wherein the hydroxy group being reacted is either a primary or secondary hydroxy group, with a carboxylic anhydride in the presence of carboxylesterase as a catalyst in an organic solvent.

2. The process as claimed in claim 1, wherein the carboxylic anhydride has the molecular weight below 350 and can dissolve in the organic solvent.

3. The process as claimed in claim 2, wherein the carboxylic anhydride is a compound of the formula:

##STR8## wherein R and R₁ respectively is hydrogen, an alkyl, alkenyl, alkynyl, aryl or aralkyl group.

4. The process as claimed in claim 3, wherein R and R₁ are the same.

5. The process as claimed in claim 4, wherein R and R₁ are a straight-chain or branched alkyl of 1 to 5 carbon atoms or phenyl.

6. The process as claimed in claim 1, wherein the hydroxy compound is an organic compound containing 1 to 10 hydroxy groups which has the molecular weight below 1,500 and which can dissolve in the organic solvent.

7. The process as claimed in claim 6, wherein the hydroxy compound is an organic compound of the formula:

R₂ OH wherein R₂ is an alkyl, alkenyl, alkynyl, aryl, aralkyl or heterocyclic group which may be substituted.

8. The process as claimed in claim 1, wherein the hydroxy compound is lower (C_2-4) alcohols, lankacidin C or maridomycin.

9. The process as claimed in claim 1, wherein the carboxylesterase is organic solvent-soluble carboxyl esterase which is modified with a polyethylene glycol derivative.

10. The process as claimed in claim 9, wherein the organic solvent-soluble carboxylesterase is one which is modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine.

11. The process as claimed in claim 1, wherein the carboxylesterase is in the form of the culture filtrate of a carboxylesterase-producing microorganism.

12. The process as claimed in claim 1, wherein the organic solvent can form a two phase system with water.

13. The process as claimed in claim 12, wherein the organic solvent is a ketone or an ester.

14. The process as claimed in claim 1, wherein the organic solvent is methyl ethyl ketone, methyl n-propyl ketone, methyl n-butyl ketone, methyl isobutyl ketone, methyl acetate or ethyl acetate.

15. The process as claimed in claim 1, wherein the reaction is conducted at a temperature in the range of 5°

to 90°

C. and the pH value in the range of from 2 to 10.

16. The process as claimed in claim 7, wherein the hydroxy compound is an alcohol, phenol, 8-quinolinol, hydroxypiperidine, antibiotic, fibrostatin E or fibrostatin F.

17. A process for producing lankacidin A which comprises reacting lankacidin C with acetic anhydride in the presence of carboxylesterase as a catalyst, said carboxyl esterase being in the form of a culture filtrate of Streptomyces rochei var. volubilis, in methyl isobutyl ketone.

18. A process for producing a carboxylic acid ester which comprises reacting a lankacidin antibiotic having a hydroxy group at the 14-position or a maridomycin antibiotic having a hydroxy group at the 9-position with a carboxylic anhydride to esterify said hydroxy group in the presence of carboxylesterase originating from Streptomyces rochei var. volubilis.

19. A process for producing a carboxylic acid ester which comprises reacting a primary or secondary C_2-4 alcohol, a lankacidin antibiotic having a hydroxy group at the 14-position or a maridomycin antibiotic having a hydroxy at the 9-position, with a carboxylic anhydride to esterify said hydroxy group, in the presence of carboxylesterase originating from Streptomyces rochei var. volubilis, in an organic solvent.