Method for preparing (R)-6-hydroxy-8-chlorine octanoic acid ethyl by enzyme resolution

A technology of ethyl chlorooctanoate and hydroxyl, applied in the field of biocatalysis, can solve problems such as complex operation process, unfavorable safety, and poor effect, and achieve the effect of environmental friendliness, product safety, and easy separation

Inactive Publication Date: 2007-10-31
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Chemical methods for splitting racemates often have poor results, low yields, and complicated operations. Some chemical splitting agents even contain toxicity (such as crown ethers), which is not conducive to safety.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 Screening of enzymes for resolution of racemic ethyl 6-hydroxy-8-chlorooctanoate

[0031]The following lipases were screened: lipase Novozym 435 (from Candida antarctica) was purchased from Novozymes; lipase CRL (from Candida rugosa), lipase L-3124 and L-3126 (from Porcine pancreas), Lipase IM (from Mucor miehei), LipaseF-AP (from Rhizopus oryzae) were purchased from Sigma; Lipase MY (from Pseudomonassp.) was purchased from Meito Sangyo, Japan; Lipase PS-D (from Pseudomonas sp.) was purchased From Amano, Japan; alkaline lipase (from Penicillium expansum) and penicillium lipase (from Peniciline sp.) were purchased from Shenzhen Lvweikang Bioengineering Co., Ltd. Racemic ethyl 6-hydroxy-8-chlorooctanoate was purchased from Changshu Wanxing Chemical Co., Ltd.; other reagents are commercially available analytically pure.

[0032] Add the substrate 6-hydroxy-8-chlorooctanoic acid ethyl ester at a concentration of 45mmol / L, use a pH 7.0 phosphate buffer system, add 10g / ...

Embodiment 2

[0035] Example 2 The effect of shaker speed on the resolution of ethyl 6-hydroxy-8-chlorooctanoate by Lipase PS-D

[0036] Add the substrate 6-hydroxy-8-chlorooctanoic acid ethyl ester at a concentration of 45mmol / L, use a pH 7.0 phosphate buffer system, add 10g / L lipase Lipase PS-D to start the reaction, respectively, at different speeds at 30℃ The reaction was performed on a water bath shaker for 1 hour. After the reaction was completed, the lipase was removed by centrifugation to obtain the supernatant. The supernatant was extracted with ethyl acetate, and the organic phase was taken with an appropriate amount of anhydrous MgSO 4 After drying overnight, after filtering, the content and enantiomeric excess of ethyl (R)-6-hydroxy-8-chlorooctanoate were analyzed by gas chromatography, and the initial rate of the enzyme reaction was calculated. The results are shown in Table 2.

[0037] Shaker speed (r / min)

[0038] It can be seen from Table 2 that the initial speed of th...

Embodiment 3

[0039] Example 3 The effect of reaction temperature on Lipase PS-D catalytic resolution of ethyl 6-hydroxy-8-chlorooctanoate

[0040] The reaction system was prepared according to Example 2, and reacted for 1 hour in a 170r / min water bath shaker at different temperatures. After the reaction was completed, the lipase was removed by centrifugation to obtain the supernatant. The supernatant was extracted with ethyl acetate, and the organic phase was taken with an appropriate amount of anhydrous MgSO 4 It was dried overnight, filtered and analyzed by gas chromatography for the content and enantiomeric excess of ethyl (R)-6-hydroxy-8-chlorooctanoate. The results are shown in Table 3.

[0041] Temperature

[0042] It can be seen from Table 3 that the initial reaction rate and substrate conversion rate both increase with the increase of reaction temperature. However, the enantioselectivity of the enzyme-catalyzed hydrolysis reaction decreases with the increase of the reaction t...

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PUM

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Abstract

The invention discloses a preparing method of (R)-6-hydroxyl group-8-chlorin octoic acid carbethoxyl in biological catalysis technical domain, which comprises the following steps: sieving lipase with better stereoselectivity; optimizing a series of inversion conditions of enzyme resolution such as rotator speed of shaker, reaction temperature, reaction pH, bottom matter density and addition of surface activator or organic co-solvent; setting optical purity of product at 93. 8% and receiving ratio at 46. 7%; utilizing solubility difference of 6-hydroxyl group-8-chlorin octoic acid carbethoxyl and 6-hydroxyl group-8-chlorin octoic acid under different pH; proceeding primary separation for the product; getting the rough product with content of (R)-6-hydroxyl group-8-chlorin octoic acid carbethoxyl at 83. 4% and extraction receive rate at 92. 4%. This invention provides a new approach for (R)-lipoic acid preparation.

Description

Technical field [0001] A method for preparing (R)-6-hydroxy-8-chlorooctanoic acid ethyl ester by enzymatic resolution, that is, lipase splitting racemic 6-hydroxy-8-chlorooctanoic acid ethyl ester to prepare (R)-lipoic acid chiral The method of intermediate (R)-6-hydroxy-8-chlorooctanoic acid ethyl ester belongs to the technical field of biocatalysis. Background technique [0002] The main purpose of ethyl 6-hydroxy-8-chlorooctanoate is to synthesize lipoic acid. R-lipoic acid (Lipoic acid) belongs to the vitamin B compound. It is a natural product with biological activity. It is widely used in medicine, health care products, food additives and cosmetics. Its antioxidant capacity is 400 times that of vitamin E. , Has great market potential. Lipoic acid can enter the brain through the brain blood barrier and is particularly effective in removing free radical toxins from various organs of the head. It can protect the brain and eyes from pollution toxins and infections, relieve brai...

Claims

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Application Information

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IPC IPC(8): C12P7/62C12P41/00
Inventor 孙志浩郑璞倪晔韩丽杨倩
Owner JIANGNAN UNIV
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