Process for the enzymatic production of carnitine from beta-lactones

Patent metadata

Field	Value
Publication number	US-9523106-B2
Application number	US-201213557922-A
Country	US
Kind code	B2
Filing date	Jul 25, 2012
Priority date	Jul 27, 2011
Publication date	Dec 20, 2016
Grant date	Dec 20, 2016

Abstract

Subject of the invention is a process for the production of L-carnitine, wherein a β-lactone, which is a 4-(halomethyl)oxetane-2-one, is converted into L-carnitine, wherein the process comprises an enzymatic conversion of the β-lactone into (R)-4-halo-3-hydroxybutyric acid or (R)-4-halo-3-hydroxybutyric acid ester.

First claim

The invention claimed is:

1. A process for the production of L-carnitine, wherein a β-lactone, which is a 4-(halomethyl)oxetane-2-one, is converted into L-carnitine, wherein the process comprises enzymatic conversion of the β-lactone into (R)-4-halo-3-hydroxybutyric acid, wherein the enzymatic conversion is carried out with a lipase in an aqueous medium, the lipase having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, wherein the enantiomeric purity of the (R)-4-halo-3-hydroxybutyric acid is at least 95% e.e., and conversion of (R)-4-halo-3-hydroxybutyric acid into L-carnitine with trimetylamine.

2. The process of claim 1 , wherein the β-lactone is a racemate.

3. The process of claim 2 , wherein an enantiomeric excess of the (R)-4-halo-3-hydroxybutyric acid is obtained.

4. The process of claim 1 , wherein the enzymatic conversion is carried out in a two phase solution, wherein (R)-4-halo-3-hydroxybutyric acid is enriched in the aqueous phase.

5. The process of claim 1 , wherein after enzymatic conversion, residual β-lactone is removed from the solution.

6. The process of claim 5 , wherein the residual β-lactone is removed by extraction with a solvent.

7. The process of claim 1 , wherein the lipase is from Candida, Pseudomonas, Aspergillus, Bacillus or Thermomyces.

8. The process of claim 1 , wherein the lipase is from Pseudomonas cepacia, Pseudomonas fluorescens , or Candida antarctica.

9. The process of claim 1 , wherein the enzymatic conversion is carried out at a temperature between 0° C. and 50° C., and/or wherein the enzymatic conversion is carried out in an aqueous solution comprising 0.1 to 10 weight % β-lactone.

10. The process of claim 9 , wherein the enzymatic conversion is carried out at a temperature between 20° C. and 40° C., and/or wherein the enzymatic conversion is carried out in aqueous solution comprising 0.1 to 10 weight % β-lactone.

11. The process of claim 1 , in which the β-lactone is synthesized in a preceding step in a [2+2] cycloaddition of ketene and an aldehyde of the formula X-CH2-CHO, wherein x is selected from Cl, Br and I.

12. The process of claim 1 , wherein the total yield of (R)-4-halo-3-hydroxybutyric acid in the enzymatic conversion is between 40% and 50%, based on the total initial amount of β-lactone.

13. The process of claim 1 , wherein the reaction time of the enzymatic conversion of the β-lactone into (R)-4-halo-3-hydroxybutyric acid is less than 10 hours.

Assignees

• Klegraf Ellen
• Avi Manuela
• Lonza Ag

Inventors

• Klegraf Ellen
• Avi Manuela

Classifications

• C12P7/42

  Hydroxy-carboxylic acids · CPC title

• C12P41/005

  by esterification of carboxylic acid groups in the enantiomers or the inverse reaction · CPC title

• C12P13/007 Primary

  Carnitine; Butyrobetaine; Crotonobetaine · CPC title

• C12P7/62

  Carboxylic acid esters · CPC title