Synthesis method of R-lipoic acid

Abstract

The invention relates to a synthesis method of R-lipoic acid, which comprises the following steps: mixing N-(5-bromopentyl) phthalimide with zinc powder, lithium chloride, trimethylchlorosilane, 1, 2-dibromoethane and tetrahydrofuran, reacting to generate a zinc bromide intermediate, and then carrying out substitution reaction on 3-{[2-(trimethylsilyl) ethyoxyl] methoxy} propionyl chloride and the zinc bromide intermediate; carrying out hydrazinolysis reaction on the obtained intermediate-1; carrying out catalytic oxidation reaction on the obtained intermediate-2; carrying out esterification reaction on the obtained intermediate-3; introducing candida parapsilosis into a fermentation medium for multiplication culture, suspending obtained resting cells in a buffer aqueous solution, and adding the obtained intermediate-4 for an enzyme-catalyzed chiral reduction reaction; carrying out a deprotection reaction on the obtained intermediate-5; carrying out chlorination reaction on the obtained intermediate-6; carrying out cyclization reaction on the obtained intermediate-7; and carrying out hydrolysis reaction on the obtained intermediate-8 to obtain a finished product.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and in particular relates to a synthesis method of R-lipoic acid. Background technique [0002] α-lipoic acid is a vitamin-like compound that can eliminate free radicals that accelerate aging and cause disease. It is both water-soluble and fat-soluble. Universal antioxidant drug. α-lipoic acid has a certain effect on the treatment of many diseases such as liver disease, diabetes, HIV virus, tumor, nervous system degeneration, radiation injury, arsenic, mercury, cadmium and other heavy metal poisoning, for example, it can assist in the treatment of type II diabetes and improve Pancreatic islets function in glucose metabolism, protect nerve cells, prevent cataracts, prevent muscle damage and so on. [0003] As shown in the following chemical structural formula, in the molecular structure of α-lipoic acid, there is a chiral carbon in position 3 of the dithiolane ring, whi...

AI Technical Summary

Problems solved by technology

Although people have developed a racemization method for S-lipoic acid, the conversion of S-lipoic acid into cyclic lipoic acid is relatively harsh on actual production conditions, corrosive to equipment, and the yield is low, resulting in expensive production costs; The second is to use 6,8-dihydroxyoctanoic acid methyl ester or 6-hydroxy-8-chlorooctanoic acid methyl ester as the starting material to make mesylate, and then stereoselectively form R-lipoic acid. The process of this method is relatively complicated , especially not easy to obtain pure product; the third is to hydrolyze racemic 6,8-dichlorooctanoic acid ethyl ester into (±) dichlorooctanoic acid, and then use a resolving agent to split, rethio and cyclization, the method is basically Can save costs, but because about 50% of S-(-)-6,8-dichlorooctanoic acid is still not utilized, the cost is higher

[0006] The synthesis methods of R-lipoic acid in the prior art, including the above-mentioned three methods, all have high cost, low yield and large consumption of raw materials, which cannot meet the requirements of industrial scale-up production, and due to high waste discharge. Disadvantages of not meeting the requirements of green production

Images