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Racemization method of S-lipoic acid and preparing method of R-lipoic acid

A technology of racemization and lipoic acid, applied in the direction of organic chemistry methods, chemical instruments and methods, organic racemization, etc., can solve the problems of relatively harsh production conditions, difficult to obtain pure products, high production costs, etc., and achieve good results Industrial applicability, reducing safety hazards, avoiding the effect of processing

Active Publication Date: 2012-05-09
JIANGSU TOHOPE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] ① Use 6,8-dihydroxyoctanoic acid ethyl ester or 6-hydroxy-8-chlorooctanoic acid methyl ester as the starting material to make mesylate, and then split into R-(+)-lipoic acid (US 5869713, G.Bringmann, J.Paust.Z.Naturforshung 546, 661-665, 999), the process is more complicated, and it is not easy to obtain pure products
[0008] ② Hydrolyze racemic 6,8-dichlorooctanoic acid ethyl ester into (±) 6,8-dichlorooctanoic acid (DCA), react with (-) ephedrine to form a salt, split, and then undergo thiolation and cyclization And the finished product (Acker et al., J.Am.Chem.Soc., 76,6483,1954), this method still has 50% S-(-)-6,8-dichlorooctanoic acid not utilized, and the cost is higher
[0009] ③Using 6,8-dichlorooctanoic acid ethyl ester as the starting material, through thiolation, cyclization, and hydrolysis to obtain racemic lipoic acid, and then use a resolving agent to resolve to obtain R-(+)-lipoic acid, The yield of this step is about 45%, and S-(-)-lipoic acid is racemized under high pressure (US 5621117), but the requirements for actual production conditions are relatively harsh, resulting in high production costs

Method used

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  • Racemization method of S-lipoic acid and preparing method of R-lipoic acid
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Examples

Experimental program
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Effect test

Embodiment 1

[0042] Weigh 100g of racemic lipoic acid, dissolve it in 500g of toluene at 60°C, slowly add 50g of R-(+)-phenethylamine dropwise, and finish dropping in about 1.5 hours. Cool slowly to 0-10°C, filter, and wash the filter cake with toluene to obtain about 110 g of R-(+)-lipoic acid phenethylamine salt. Dissolve the above product in 500g toluene at 40°C, add 10% dilute sulfuric acid solution dropwise until the pH value is 2-3, let it stand for half an hour, and then remove the acid water. The toluene layer was washed with water until neutral, dried over anhydrous sodium sulfate, and filtered. The toluene was recovered by distillation under reduced pressure, and the obtained crude product was recrystallized with 600g of cyclohexane to obtain 45g of R-(+)-lipoic acid product, with a yield of 45%.

[0043] The filtered mother liquor was acidified with 10% dilute sulfuric acid to a pH value of 2-3, washed, concentrated toluene, crystallized and filtered to obtain about 50g of S-(-...

Embodiment 2

[0046] About 50g of S-(-)-lipoic acid was prepared in Example 1, dissolved in 100ml of toluene, heated to reflux at a reflux temperature of 110°C for 22 hours, and the solvent was concentrated. Recrystallized with cyclohexane to obtain 45g, =-0.072°.

[0047]

Embodiment 3

[0049]According to Example 1, about 50 g of S-(-)-lipoic acid was prepared, dissolved in 200 ml of DMF, heated to reflux at a reflux temperature of 153° C. to 156° C., refluxed for 22 hours, and concentrated the solvent. Recrystallized with cyclohexane to obtain 43g, =-0.043°.

[0050]

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Abstract

The invention discloses a racemization method of S-(-)-lipoic acid, the S-(-)-lipoic acid is dissolved in a solvent, heated at 110-220 DEG C under a normal pressure for backflow for at least 15 hours; after the solvent is concentrated, racemization lipoic acid is obtained by crystallization; and the prepared racemization lipoic acid is + / -1 degrees. The invention further relates to a preparing method of R-(+)-lipoic acid, which is characterized in that: using the racemization lipoic acid as raw material; using R-(+)-phenylethy lamine to split enantiomer; racemizing the split S-(-)-lipoic acidas raw material for reuse. The method disclosed by the invention racemizes the S-(-)-lipoic acid, and improves the preparing method of the R-(+)-lipoic acid by a racemization method, so that technology is simplified, yield is obviously increased and production cost is reduced; the racemization method of the S-lipoic acid and the preparing method of the R-lipoic acid have excellent industrial application value.

Description

technical field [0001] The present invention relates to a method for the resolution and racemization of optical isomers of the optically active compound lipoic acid, in particular to a method for the racemization of L-S-(-)-lipoic acid, and for D-R-(+) - Process for the preparation of lipoic acid. Background technique [0002] Alpha lipoic acid (ALA for short), chemical name 1, 2-dithiolane-3-pentanoic acid, belongs to vitamin B group compounds, has the functions of scavenging free radicals and active oxygen (anti-oxidation), chelating metal ions, It can regenerate other antioxidants, etc. It is mainly used clinically to treat diabetes and its complications, ischemia-reperfusion, degenerative neuropathy, radiation damage and other diseases. Because of its safety, reliability and definite curative effect, lipoic acid is widely used in medicine, health care, beauty and other fields. [0003] R-(+)-lipoic acid (1) and S-(-)-lipoic acid (2) are a pair of enantiomers of lipoic ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D339/04C07B55/00C07B57/00
Inventor 邹振荣
Owner JIANGSU TOHOPE PHARMA
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