Scopolamine butylbromide (link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/scopolamine-butylbromide-cas-149-64-4.html) is a drug widely used to treat gastrointestinal symptoms, and its chemical structure is similar to Scopolamine hydrobromide. For pharmaceutical manufacturers, finding an efficient and feasible synthesis method can not only greatly reduce production costs, but also ensure product quality and yield.
Traditional chemical synthesis method:
1.1 Synthetic route one:
The synthetic route comes from a research report ("Synthesis of buscopan derivatives"), the main steps are as follows:
Step 1: Reaction of 2-bromoisopropylacetophenone with N-methyl-2-pyridinecarboxamide:
Mix 2-bromoisopropylacetophenone with N-methyl-2-pyridinecarboxamide and react at 85°C for several hours in the presence of cesium chloride to obtain the product.
Step 2: Reaction of 2-bromoisopropyl-N-methyl-2-pyridinecarboxamide with propylene oxide:
The above product is mixed with propylene oxide and stirred at room temperature in the presence of sodium hydroxide for several hours to obtain Scopolamine butylbromide.
The advantage of this synthetic route is that the reaction conditions are mild, and there is no need to use too many toxic and harmful solvents and reagents. However, the separation and purification steps of this method are relatively cumbersome, and the yield is not ideal.
1.2 Synthetic route two:
The synthetic route is derived from a patent document (US Patent 4418109 A), and the main steps are as follows:
Step 1: Reaction of cis-4-hydroxy-3-methoxyphenylacetic acid with 2,3-dibromopropionyl bromide:
cis-4-hydroxy-3-methoxyphenylacetic acid was mixed with 2,3-dibromopropionyl bromide and reacted for several hours at room temperature in the presence of ethanol to give 2-(4-hydroxy-3-methoxy phenylacetic acid)-2,3-dibromopropyl ester.
Step 2: Recrystallization of 2-(4-hydroxy-3-methoxyphenylacetic acid)-2,3-dibromopropyl ester:
The above product was recrystallized to obtain a product with higher purity.
Step 3: Reaction of 2-(4-hydroxy-3-methoxyphenylacetic acid) propionamidine with metabromic acid:
Mix 2-(4-hydroxy-3-methoxyphenylacetic acid)propionamidine with metabromide and react at room temperature for several hours in the presence of ethanol to obtain Scopolamine butylbromide.
The advantage of this synthetic route is that the separation and purification steps are optimized, the product has high purity, and the yield is relatively ideal. However, the reaction conditions are relatively harsh and require a certain chemical laboratory basis.
Enzymatic synthesis method:
2.1 Synthetic route three:
The synthetic route comes from a research report published in Journal of Molecular Catalysis B: Enzymatic ("Enzymatic synthesis of scopolamine butyl bromide via thermophilic esterase"), the main steps are as follows:
Step 1: Synthesis of 2-(4-hydroxy-3-methoxyphenylacetic acid) propionyl chloride:
Mix 2-(4-hydroxy-3-methoxyphenylacetic acid) with propionyl chloride and react at room temperature for several hours in the presence of a catalyst to obtain 2-(4-hydroxy-3-methoxyphenylacetic acid) propionyl chloride acid chloride.
Step 2: Reaction of 2-(4-hydroxy-3-methoxyphenylacetic acid) propionyl chloride with n-butylammonium bromide.
The above product is mixed with n-butylammonium bromide, and in the presence of phosphate buffer, under the appropriate temperature and pH conditions, the enzyme Thermomyces lanuginosus lipase (TLL) with high thermal stability is used to catalyze the reaction to obtain Scopolamine butylbromide .
Compared with the first two chemical synthesis methods, this synthetic route has milder reaction conditions and better selectivity and yield. However, this method has high requirements for catalysts and enzymes, and certain process optimization is required.
Synthesis method comparison and summary:
Judging from the several synthetic methods of Scopolamine butylbromide introduced above, traditional chemical synthesis methods and enzymatic synthesis methods have their own advantages and disadvantages. The traditional chemical synthesis method is simple and easy, but the reaction conditions are relatively harsh, and the separation and purification steps are cumbersome. The enzymatic synthesis method has mild reaction conditions, high selectivity and yield, but requires high enzyme activity and catalyst purity, and further process optimization is required.
In conclusion, the synthetic method of Scopolamine butylbromide still faces some challenges and difficulties. However, with the development of biotechnology and chemical synthesis technology, it is believed that more efficient, environmentally friendly, and feasible synthesis methods will be discovered and promoted, thereby providing better possibilities for the large-scale industrial production of Scopolamine butylbromide.
Scopolamine butylbromide is a complex organic compound with the molecular formula C21H30BrNO4. It belongs to the dimethyloxymuscarinic class of drugs, similar to atropine, but compared with atropine, its bromide ion replaces the hydroxyl group.
1. Molecular structure:
The molecular structure of Scopolamine butylbromide contains a carboxylic acid monoester structure (COOCH2CH2CH2CH3) and a benzyloxycarbonyl structure (C6H5CH2OCO) containing a bromine atom. Among them, the benzyl group and the methyl group are connected on the carbonyl to form a six-membered ring, and the six-membered ring is connected to another five-membered ring. There is a maleyl group with three hydrogen atoms, one amino group and one oxygen atom on the five-membered ring. In the imine structure, the atoms in the four different positions of the five-membered ring are connected to different groups, as shown in the figure:
This molecular structure enables Scopolamine butylbromide to have an anticholinergic effect similar to that of atropine, and at the same time, the substitution of bromine atoms reduces the central effects of atropine drugs. In addition, the structure of the five-membered ring part also endows Scopolamine butylbromide with certain stability.
2. Anticholinergic pharmacological effects:
Scopolamine butylbromide is an anticholinergic drug, and its effect is mainly to weaken the effect of acetylcholine by competitively antagonizing the action of acetylcholine on M1-M5 receptors. In the gastrointestinal tract, Scopolamine butylbromide can relax smooth muscle, reduce water secretion, and have therapeutic effects on indigestion, abdominal discomfort and other diseases. In the motor system, Scopolamine butylbromide can relieve muscle spasm, and has a certain effect on alleviating motor system diseases such as spastic torticollis. In addition, in the respiratory system, Scopolamine butylbromide can also be used as a bronchodilator.
3. Pharmacokinetics:
Scopolamine butylbromide can enter the body through the intestinal tract and the blood-brain barrier after oral administration or injection. In the gastrointestinal tract, it is absorbed relatively quickly, reaching peak blood levels in about 1-2 hours, and reaching peak blood levels in 0.5-1 hours after injection. Oral Scopolamine butylbromide is mainly metabolized by the liver, where it is acylated or hydroxylated to generate corresponding metabolites, which are then excreted out of the body by the kidneys or bile. Injection of Scopolamine butylbromide is more easily metabolized and excreted by the kidneys. In general, the metabolism and elimination of Scopolamine butylbromide in the body are relatively rapid, and its half-life is between 2-4 hours.
In summary, Scopolamine butylbromide is an organic compound with complex structure and strong biological activity, which has various anticholinergic effects. Its molecular structure contains benzyloxycarbonyl structure and carboxylic acid monoester structure, which is an important basis for its anticholinergic pharmacological properties. In terms of pharmacokinetics, Scopolamine butylbromide has good bioavailability and metabolic effects, and is widely used in clinical practice.