CN115521353A - Method for preparing diosgenin derivative by adopting dimethyl carbonate - Google Patents
Method for preparing diosgenin derivative by adopting dimethyl carbonate Download PDFInfo
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- CN115521353A CN115521353A CN202111345504.3A CN202111345504A CN115521353A CN 115521353 A CN115521353 A CN 115521353A CN 202111345504 A CN202111345504 A CN 202111345504A CN 115521353 A CN115521353 A CN 115521353A
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- diosgenin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
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Abstract
The invention relates to the field of C07D organic compound synthesis, and more particularly provides a method for preparing diosgenin derivatives by using dimethyl carbonate. Compared with the prior art, the novel method for preparing the diosgenin derivative has the advantages of simple and easily obtained raw materials, safety, no stimulation, environmental friendliness, simplicity in operation and high product yield, and provides a novel strategy for methylation reaction of the diosgenin.
Description
Technical Field
The invention relates to the field of C07D organic compound synthesis, and more particularly provides a method for preparing diosgenin derivatives by using dimethyl carbonate.
Background
Fused ring-based compounds are widely present in natural products, and are used in various fields because of their diversified biological activities. For example, ruscogenin A has biological activities of anti-inflammation, anti-thrombosis, anti-tumor and the like, and is widely applied to the field of medicines; the diosgenin B can be used for protecting the spinal cord from being damaged, can be used for pharmacological experiments and identification, has the function of reducing blood fat, and has potential application value in the field of medical research; rhizoma paridis saponin C has anti-tumor, antivirus and blood pressure lowering effects, and can be used for treating infectious diseases and cancer.
Diosgenin D plays a significant role in the field of medicine because of its biological activities of resisting vascular calcification, reducing serum cholesterol, promoting the secretion of serum antibody lgG from human body, etc. In recent years, extensive research by researchers finds that the methylated product of diosgenin can be used as an important precursor of a vaccine carrier, and has potential application value in the field of vaccine carriers. At present, the method for synthesizing the dioscin methylated product still has the problems of poor safety and environmental pollution.
In 2009, "Molecular Microbiology" 74 (5), 1031-1043, a method for methylating diosgenin is disclosed, in which methyl iodide is used as methylating agent, sodium hydride is used as base, and the corresponding target product is obtained at room temperature for 24h, but in the method, sodium hydride is used as base, the water content in the reaction system needs to be strictly controlled, otherwise the reaction is violent, and the reaction risk is increased sharply.
Chinese patent publication No. CN100357310C discloses a method for synthesizing cholesterol and its intermediate, in which diosgenin is used as a raw material, dimethyl sulfate is used as a methylation product, and sodium hydride is used as an alkali to react to obtain a diosgenin methylation product, but the method adopts highly toxic dimethyl sulfate, which has serious threat to the health of operators and causes environmental pollution, and does not conform to the green synthesis concept of "green environmental protection"; meanwhile, sodium hydride is used as a catalyst, so that potential safety hazards exist, and industrial production is not facilitated.
Therefore, the method for synthesizing the dioscin methylated product, which is green, pollution-free, high in safety, high in product yield and high in purity, has potential application value in the field of medical intermediates.
Disclosure of Invention
In order to solve the technical problems, the invention provides a method for preparing diosgenin derivatives by using dimethyl carbonate, which comprises the steps of taking diosgenin as a reaction substrate, reacting with an alkaline compound containing a metal element and a methylation reagent with the carbon atom number of 1-5 for 1-5h under the conditions that the reaction temperature is 100-300 ℃ and the reaction pressure is 0.1-1MPa, cooling, filtering, and recrystallizing by using an organic reagent to obtain the diosgenin derivatives.
The structural formula of the diosgenin is shown as a formula (1):
the structural formula of the diosgenin derivative is shown as a formula (2):
in a preferred embodiment of the present invention, the metal element-containing basic compound includes at least one of cesium carbonate, sodium carbonate, lithium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, and lithium hydroxide.
In a preferred embodiment of the present invention, the methylating agent having 1 to 5 carbon atoms includes at least one of methyl iodide, methyl bromide, dimethyl carbonate and methyl trifluoromethanesulfonate.
As a preferable technical scheme of the invention, the weight ratio of the diosgenin, the methylating agent with 1-5 carbon atoms and the alkaline compound containing the metal element is (30-60): (150-300): (1-10).
As a more preferable technical scheme, the weight ratio of the diosgenin, the methylation reagent with the carbon number of 1-5 to the alkaline compound containing the metal element is (40-50): (200-280): (1-5).
As a most preferred technical scheme of the invention, the weight ratio of the diosgenin, the methylating agent with 1-5 carbon atoms and the alkaline compound containing the metal element is 45:260:1.
as a preferred technical scheme of the invention, the reaction temperature is 150-250 ℃.
In a more preferred embodiment of the present invention, the reaction temperature is 170 ℃.
As a preferable technical scheme of the invention, the reaction pressure is 0.1-0.5MPa.
In a more preferred embodiment of the present invention, the reaction pressure is 0.3MPa.
The applicant follows the concept of 'green and environment-friendly' organic chemical synthesis, and finds that when dimethyl carbonate is used for replacing dimethyl sulfate as a methylation reagent for preparing the diosgenin derivative, a water-sensitive catalyst is not used, so that the danger of a synthesis process is greatly reduced, and the harm of reaction raw materials to the environment and operators in the actual preparation process is effectively relieved. In order to solve the above technical problems, the present application finds that when a micro-pressure is added to a reaction system, especially when the pressure is 0.3MPa, and the reaction temperature is 170 ℃, the yield of the diosgenin derivative can be significantly improved. The applicant guesses the possible reason because, when the reaction temperature and pressure of the system are strictly controlled, the compatibility between the diosgenin and the dimethyl carbonate in the system can be improved, the molecular migration rate of each component in the system is enhanced, the nucleophilicity of the diosgenin is enhanced, the methylation reaction process of the dimethyl carbonate and the diosgenin is improved, and the yield of the diosgenin derivatives is improved.
As a preferred technical solution of the present invention, the organic solvent includes at least one of methanol and ethanol.
Compared with the prior art, the invention has the following beneficial effects:
1. the method for preparing the diosgenin derivative adopts dimethyl carbonate as a methylation reagent of diosgenin, avoids using a catalyst with high sodium hydride risk coefficient and a methylation reagent with high toxicity of dimethyl sulfate, obtains the corresponding diosgenin derivative at a yield of 95-99%, provides a new strategy for synthesizing the diosgenin derivative, simultaneously uses the dimethyl carbonate as the methylation reagent and a reaction solvent in a body system, does not need to additionally add the reaction solvent to the system, improves the conversion rate of a reaction substrate, obviously improves the utilization rate of raw materials and reduces the production cost;
2. the method for preparing the diosgenin derivative comprises the following steps of when diosgenin is used as a reaction substrate, dimethyl carbonate is used as a methylation reagent with the carbon atom number of 1-5, potassium carbonate is used as an alkaline compound containing a metal element, and the weight ratio of the diosgenin to the dimethyl carbonate to the potassium carbonate is 45:260:1, the potassium carbonate has the best catalytic complexing effect on reactants, the methylation reaction process of the diosgenin and dimethyl carbonate in the system is promoted, and the conversion rate of the diosgenin is improved;
3. according to the method for preparing the diosgenin derivative, when the reaction temperature is controlled at 170 ℃ and the reaction pressure is 0.3MPa, the problem that the methylation effect of the dimethyl carbonate serving as a methylation reagent on the diosgenin is poor is effectively solved, the stability and the safety of a system are ensured, the conversion rate of the diosgenin is further improved, the yield and the purity of the diosgenin derivative are improved, the application range of the dimethyl carbonate serving as the methylation reagent in organic synthesis is expanded, and a new strategy is provided for the methylation reaction of the diosgenin;
4. according to the method for preparing the diosgenin derivative, when the reaction time is 4 hours, the high conversion rate of the diosgenin in the system is ensured, meanwhile, the generation of byproducts in the reaction is reduced, the complexity of the reaction system is reduced, the difficulty of post-treatment of the product is reduced, and the purity of the product is improved;
5. compared with the prior art, the method for preparing the diosgenin derivative has the advantages that on the premise of ensuring high conversion rate of the diosgenin, the preparation raw materials are simple and easy to obtain, are non-toxic and pollution-free, environment-friendly, free of anhydrous and anaerobic treatment and simple to operate, industrial-scale large-scale production is facilitated, and meanwhile, the prepared diosgenin methylated product has potential biological activity and has potential application value in the field of medical intermediates, particularly in the field of preparation of vaccine carriers.
Detailed Description
Examples
Example 1
A method for preparing diosgenin derivative by dimethyl carbonate comprises reacting 1g diosgenin as reaction substrate with alkaline compound containing metal element and methylation reagent containing 1-5 carbon atoms at 170 deg.C and 0.3MPa for 4 hr, cooling, filtering, and recrystallizing with methanol to obtain diosgenin derivative.
The mass ratio of the diosgenin to the dimethyl carbonate to the potassium carbonate is 30:150:1.
the alkaline compound containing the metal element is potassium carbonate, and the methylating agent with the carbon atom number of 1-5 is dimethyl carbonate.
Example 2
A method for preparing diosgenin derivative by dimethyl carbonate comprises reacting 1g diosgenin as reaction substrate with alkaline compound containing metal element and methylation reagent containing 1-5 carbon atoms at 170 deg.C and 0.3MPa for 4 hr, cooling, filtering, and recrystallizing with methanol to obtain diosgenin derivative.
The weight ratio of the diosgenin to the dimethyl carbonate to the potassium carbonate is 50:300:10.
the alkaline compound containing the metal element is potassium carbonate, and the methylating agent with the carbon atom number of 1-5 is dimethyl carbonate.
Example 3
A method for preparing diosgenin derivative by dimethyl carbonate comprises reacting 1g diosgenin as reaction substrate with alkaline compound containing metal element and methylation reagent containing 1-5 carbon atoms at 170 deg.C and 0.3MPa for 4 hr, cooling, filtering, and recrystallizing with methanol to obtain diosgenin derivative.
The mass ratio of the diosgenin to the dimethyl carbonate to the potassium carbonate is 45:260:1.
the alkaline compound containing the metal element is potassium carbonate, and the methylating agent with the carbon atom number of 1-5 is dimethyl carbonate.
Comparative example 1
The embodiment of comparative example 1 is the same as example 3 except that the reaction temperature is 60 ℃.
Comparative example 2
Comparative example 2 was conducted in the same manner as in example 3 except that the reaction pressure was 0MPa.
Comparative example 3
Comparative example 3 the embodiment is the same as example 3 except that the reaction pressure is 10MPa.
Evaluation of Properties
The diosgenin derivatives prepared in examples 1-3 and comparative examples 1-3 were tested for yield.
The diosgenin derivatives prepared in examples 1-3 and comparative examples 1-3 were detected by gas chromatograph (type JC-7890, detection temperature 350 deg.C) with the data shown in Table 1, wherein the gas chromatograph is available from Qingdao PolyChuang environmental protection agency GmbH.
TABLE 1
Claims (10)
1. A method for preparing diosgenin derivatives by dimethyl carbonate is characterized in that diosgenin is used as a reaction substrate, and reacts with an alkaline compound containing a metal element and a methylation reagent with the carbon atom number of 1-5 for 1-5 hours at the reaction temperature of 100-300 ℃ and the reaction pressure of 0.1-1MPa, then the obtained product is cooled and filtered, and is recrystallized by an organic reagent to obtain the diosgenin derivatives;
the structural formula of the diosgenin is shown as a formula (1):
the structural formula of the diosgenin derivative is shown as a formula (2):
2. the method of claim 1, wherein the alkali compound containing metal element comprises at least one of cesium carbonate, sodium carbonate, lithium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, and lithium hydroxide.
3. The method of claim 1, wherein the methylating agent with 1-5 carbon atoms comprises at least one of methyl iodide, methyl bromide, dimethyl carbonate, and methyl trifluoromethanesulfonate.
4. The method for preparing diosgenin derivatives according to any one of claims 1-3, wherein the weight ratio of diosgenin, methylating agent with 1-5 carbon atoms and alkaline compound containing metal element is (30-60): (150-300): (1-10).
5. The method for preparing diosgenin derivatives according to claim 4, wherein the weight ratio of diosgenin, methylating agent with 1-5 carbon atoms to alkaline compound containing metal element is (40-50): (200-280): (1-5).
6. The method for preparing diosgenin derivatives according to claim 1, wherein the reaction temperature is 150-250 ℃.
7. The method for preparing diosgenin derivatives according to claim 1 or 6, wherein the reaction temperature is 170 ℃.
8. The method of claim 1, wherein the reaction pressure is 0.1-0.5MPa.
9. The method for preparing diosgenin derivatives according to claim 1 or 8, wherein the reaction pressure is 0.3MPa.
10. The method of claim 1, wherein the organic solvent comprises at least one of methanol and ethanol.
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| CN202111345504.3A CN115521353A (en) | 2021-11-15 | 2021-11-15 | Method for preparing diosgenin derivative by adopting dimethyl carbonate |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1772760A (en) * | 2005-10-08 | 2006-05-17 | 苏州大学 | Synthesis process of chlesterol and its intermediate |
| CN109293731A (en) * | 2018-11-22 | 2019-02-01 | 莫伟文 | A kind of preparation method of safe synthetic reaction sisal hemp saponin(e methylation product |
| CN111732625A (en) * | 2020-07-15 | 2020-10-02 | 莫伟文 | Preparation method of sisalagenin secondary glycoside methylated compound |
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2021
- 2021-11-15 CN CN202111345504.3A patent/CN115521353A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1772760A (en) * | 2005-10-08 | 2006-05-17 | 苏州大学 | Synthesis process of chlesterol and its intermediate |
| CN109293731A (en) * | 2018-11-22 | 2019-02-01 | 莫伟文 | A kind of preparation method of safe synthetic reaction sisal hemp saponin(e methylation product |
| CN111732625A (en) * | 2020-07-15 | 2020-10-02 | 莫伟文 | Preparation method of sisalagenin secondary glycoside methylated compound |
Non-Patent Citations (2)
| Title |
|---|
| KAMILA Z. ROSŁONIEC 等: "Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side-chain degradation in Rhodococcus jostii RHA1", 《MOLECULAR MICROBIOLOGY》, vol. 74, no. 5, pages 1031 - 1043 * |
| 舒婷 等: "碳酸二甲酯作甲基化试剂的研究进展", 《化工中间体》, no. 1, pages 20 - 22 * |
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