Methylergometrine(link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/methylergonovine-powder-cas-113-42-8.html) is a quaternary ammonium alkaloid with a chemical structure of C15H23NO2 and CAS 113-42-8. It has optical activity, and both left-handed and right-handed bodies have biological activity, with the left-handed body having stronger activity. Mainly present in ergot plants such as rye, barley, wheat, as well as other cereal crops and grasses. In ryegrass, the content of methylergometrine is relatively high, but its specific content varies depending on the type of plant, growth conditions, and processing methods. It has various biological activities. It can inhibit the growth and spread of tumor cells and can be used for the treatment and prevention of cancer. In addition, methylergometrine also has anti-inflammatory, anti immune, and antioxidant effects, which can be used to treat inflammatory diseases, autoimmune diseases, and oxidative stress-related diseases. In clinical practice, it is mainly used to treat pain symptoms such as migraine, menstrual pain, and dysmenorrhea, as well as to improve the symptoms of chronic inflammatory diseases, autoimmune diseases, and oxidative stress related diseases. It can also be used to treat tumors, in combination with other anti-tumor drugs, to improve treatment effectiveness and prolong survival.
The biological fermentation method of methyl ergosteine generally uses ergic acid as the raw material and produces methyl ergosteine through microbial fermentation.
Fermentation method for producing ergic acid:
C6H12O6 + 2H2O + O2 → 2CH2OHCHOHCOOH + energy
Preparation of methyl ergosterine through methylation reaction:
CH2OHCHOHCOOH + CH3I → CH3(CHOH)COOH +CH3OH + HI
Fermentation production of ergot acid:
1. Using wheat and other wheat crops as the main raw materials, wort is obtained after pre-treatment such as crushing, liquefaction, and saccharification.
2. Add cultured ergot bacteria into wort and ferment under suitable conditions such as temperature and pH value.
3. After fermentation, the bacterial body is filtered out to obtain a fermentation broth containing lysergic acid.
Preparation of methyl ergometrine:
1. Add an appropriate amount of solvent such as ethanol or isopropanol to the fermentation broth to dissolve lysergic acid, and add an appropriate amount of acidic reagents such as sulfuric acid or sodium hydroxide hydrochloride to adjust the pH value to acidity.
2. Add an appropriate amount of sodium nitrite to the acidic solution and react at a certain temperature for a certain time to cause the diazotization reaction between lysergic acid and sodium nitrite, generating diazonium salts.
3. Treat the diazonium salt with an appropriate amount of sodium hydroxide solution, adjust the pH value to neutral, and obtain ergometrine.
4. Under alkaline conditions, an appropriate amount of methylation reagent (such as dimethyl sulfate or iodomethane) is added to ergometrine to cause a methylation reaction of ergometrine, generating methyl ergometrine.
The semi synthetic method of methyl ergometrine is to prepare methyl ergometrine from aspirin through hydrolysis, etherification, reduction, and other reactions.
Aspirin hydrolysis:
C9H8O4 + 2H2O → C7H6O2 + C3H4O2
Preparation of aspirin methyl ether:
C7H6O2 + CH3OH → C7H7O2CH3 + H2O
Preparation of methyl ergometrine:
C7H7O2CH3 + HCHO + H2 → C8H9NO2 + CH3OH
Hydrolysis of aspirin:
1. Add an appropriate amount of water and dilute hydrochloric acid sulfuric acid to the reaction pot, stir and add aspirin, and heat to a certain temperature;
2. Add an appropriate amount of sodium hydroxide solution dropwise to fully hydrolyze aspirin;
3. Cool to room temperature, filter out sediment, wash with water until neutral, and obtain hydrolysis product.
Preparation of aspirin methyl ether:
1. Add an appropriate amount of ethanol and concentrated sulfuric acid to the reaction pot, stir and add the hydrolysis product;
2. Heat and reflux for a certain period of time to complete the reaction between the hydrolysis product and ethanol;
3. Distill and recover ethanol, wash with water until neutral, and obtain crude product;
4. Distill in a distillation tower to obtain refined aspirin methyl ether.
Preparation of methyl ergometrine:
1. Add an appropriate amount of water, hydrogen gas, and catalyst to the reaction pot;
2. Add aspirin methyl ether and heat to a certain temperature;
3. Add an appropriate amount of formaldehyde solution dropwise to cause a reduction reaction between aspirin methyl ether and formaldehyde;
4. Filter and wash with water until neutral to obtain crude methyl ergot alkaloid;
5. Distill in a distillation tower to obtain high-purity methyl ergometrine.
The total synthesis method of methyl ergometrine usually uses acetophenone as the raw material and undergoes a series of reactions to obtain methyl ergometrine.
Acetophenone sulfonation:
C6H5COCH3 + H2SO4 → C6H5CH2SO3H + H2O
Preparation of methyl ergometrine:
C6H5CH2SO3H + HCHO + NaOH → C8H9NO2+NaHSO4 + H2O
Sulfonation of acetophenone:
1. Add an appropriate amount of acetophenone and concentrated sulfuric acid to the reaction pot and heat to a certain temperature;
2. Add an appropriate amount of water dropwise to complete the sulfonation reaction of acetophenone;
3. Cool to room temperature, filter out the precipitate, wash with water until neutral, and obtain 2-acetophenone sulfonic acid.
Preparation of methyl ergometrine:
1. Add an appropriate amount of water, 2-acetophenone sulfonic acid, formaldehyde, and catalyst to the reaction pot;
2. Heat and reflux for a certain period of time to cause the reaction between 2-phenylethyl ketone sulfonic acid and formaldehyde;
3. Add an appropriate amount of alkaline solution to make the reaction solution neutral and filter out the precipitate;
4. Wash the precipitate with water, then recrystallize with ethanol to obtain the crude product of methyl ergometrine;
5. Distill in a distillation tower to obtain high-purity methyl ergometrine.
It should be noted that the reagents and equipment used in this method are commonly used laboratory equipment and reagents, and the operation process is relatively simple. The methyl ergometrine obtained by this method is a crude product that requires further processing such as crystallization and separation to obtain a higher purity product. At the same time, strict testing and control of chemical reagents and equipment are also required to ensure product quality and safety.