CAS number：1953-02-2
molecular formula：C5H9NO3S
molecular weight：163.19
EINECS number：217-778-4

English synonyms

A-MERCAPTOPROPIONYL GLYCINE;ALPHA-MERCAPTO PROPIONYL GLYCINE;LABOTEST-BB LT00451995;TIOPRONIN;N-(2-MERCAPTOPROPIONYL)GLYCINE;TOPRONIN;(2-Mercaptopropionamido)acetic acid;(2-Mercaptopropionyl)glycine

Related categories

Medical raw materials; liver disease drugs; digestive system drugs; drugs; small molecule inhibitors; chemical raw materials; raw materials; chemical biology; amino acid derivatives; pharmaceutical raw materials; biochemical reagents; superior products; ;Featured Raw Materials;Impurity Reference Substances;Raw Material Intermediates-APIs;Raw Materials;Gastrointestinal and Urinary System;Drug Impurities and Intermediates;Pharmaceutical Raw Materials;Medicine, Pesticide and Dye Intermediates;Chemical Reagents;Digestive;Pharmaceutical material and intermeidates;API;Amino Acids & Derivatives;Intermediates & Fine Chemicals;Isotope Labelled Compounds;Pharmaceuticals;Sulfur & Selenium Compounds;ACADIONE;Industrialization;APIs

Introduction

Tiopronin (tiopronin) is a new type of mercaptoglycine derivatives, the chemical name is N-(2-mercaptopropionyl)-glycine, and it is mainly used clinically to improve liver function and fatty liver in various acute and chronic hepatitis. , alcohol liver, drug-induced liver injury and detoxification of heavy metals, reduce adverse reactions of radiotherapy and chemotherapy, and prevent leukopenia caused by radiotherapy and chemotherapy.

Chemical properties

White crystalline powder with sulfur odor. Dissolved in water. The melting point is 95-97°C. Acute toxicity LD50 mice (g/kg): 2.1 intravenous injection.

Use

●  It can activate metabolic enzymes and chelate with toxic substances that hinder the activity of HS-enzymes, so it has a detoxification effect. It is mainly used for the treatment of acute and chronic hepatitis, liver cirrhosis, alcoholic liver damage and drug-induced liver damage. It can also be used for metal poisoning, chemotherapy and radiotherapy protection, urticaria, dermatitis, eczema and acne, etc.

●  It is mainly used for early senile cataracts, and can also be used for chronic hepatitis, metal poisoning, eczema, etc.

Production method

●  Propionic acid was first chlorinated with thionyl chloride, and then brominated with bromine + phosphorus to obtain α-bromopropionyl chloride (I), with a yield of 84.7%.
Glycine was dissolved in 2mol/L sodium hydroxide, cooled with an ice-salt bath, compound (I) and 2mol/L sodium hydroxide solution were added dropwise under vigorous stirring to keep the solution slightly alkaline. After adding, stir. Acidify to pH 1 with hydrochloric acid and extract with ethyl acetate. The extract was concentrated until crystals were precipitated and left to stand. The crystals were collected by filtration and dried to obtain compound (Ⅱ). The yield was. 53%.
Sodium sulfide, sublimed sulfur and water, heated and stirred to dissolve and set aside. In addition, compound (II) and sodium carbonate were dissolved in water, and the above sodium disulfide solution was added dropwise. After adding, stir. Acidify with sulfuric acid to Ph value 1, add zinc powder in batches under stirring. After adding, stir. After filtration, the filtrate was concentrated under reduced pressure until crystals were precipitated, and placed. The crystals were collected by filtration, recrystallized with ethyl acetate, and vacuum-dried to obtain tiopronin with a yield of 50.5% and a melting point of 96-97.5°C.

●  Mix glycine, sodium carbonate and water, and add 2-bromopropionyl chloride and 10% sodium carbonate solution dropwise at the same time below 0°C to keep weak alkalinity. After adding, stir. Add thiobenzoic acid, and dropwise add 15% sodium hydroxide solution to dissolve it. Stir overnight at room temperature, filter out a small amount of insoluble matter, and acidify the filtrate. The solid was collected by filtration, washed with water, 50% methanol and ethyl acetate successively, and dried to obtain compound (Ⅳ) with a yield of 76.2%.
Dissolve sodium carbonate in water, add compound (IV), stir to dissolve, add concentrated ammonia water, and stir overnight at 20°C. The solid was filtered off and washed with a small amount of water. The washing liquid and the filtrate were combined, the ammonia was removed under reduced pressure, and then acidified with 6mol/L hydrochloric acid. Concentrate under reduced pressure, add hot ethyl acetate and ethanol (1:1) mixture to dissolve. The insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure to obtain an oily substance. After cooling, a solid precipitated out and was recrystallized from ethyl acetate to obtain tiopronin with a yield of 54.9% and a melting point of 95-97°C.

●  reflux 2-chloropropionic acid and thionyl chloride together. Evaporate excess thionyl chloride and collect fractions at 109-110°C to obtain 2-chloropropionyl chloride with a yield of 91%.
Glycine, sodium carbonate and an appropriate amount of water are mixed, and under ice-salt bath cooling and vigorous stirring, an aqueous solution of 2-chloropropionyl chloride and sodium carbonate is added dropwise at the same time to maintain weak alkalinity. After adding, stir. Acidify with hydrochloric acid to a Ph value of 1, extract with ethyl acetate, dry, filter, concentrate until crystals precipitate, and set aside. The crystals were collected by filtration and dried to obtain compound (V), with a yield of 61%.
Mix sodium sulfide nonahydrate, sublimed sulfur and appropriate amount of water, heat and stir until dissolved and set aside. In addition, the compound (V), sodium carbonate and an appropriate amount of water are mixed, and the obtained sodium disulfide solution is added dropwise. After the addition is completed, react at 40-45°C. Acidify to Ph value 1 with sulfuric acid, filter. Under stirring, add zinc powder to the filtrate in batches. After adding, stir. After treatment, tiopronin was obtained with a yield of 52.2% and a melting point of 96-97.5°C.

Team Presentation