CN107746422A - Ketone contracting ammonia sulphur hydrazone of 7,22 diene of ergot steroid 3 and preparation method thereof and the application in antibacterials are prepared - Google Patents
Ketone contracting ammonia sulphur hydrazone of 7,22 diene of ergot steroid 3 and preparation method thereof and the application in antibacterials are prepared Download PDFInfo
- Publication number
- CN107746422A CN107746422A CN201710809566.2A CN201710809566A CN107746422A CN 107746422 A CN107746422 A CN 107746422A CN 201710809566 A CN201710809566 A CN 201710809566A CN 107746422 A CN107746422 A CN 107746422A
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- CN
- China
- Prior art keywords
- diene
- ketone
- ergot steroid
- steroid
- antibacterials
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
Abstract
Application the invention discloses a kind of ketone contracting ammonia sulphur hydrazone of 7,22 diene of ergot steroid 3 and preparation method thereof and in antibacterials are prepared.The ketone contracting ammonia sulphur hydrazone of 7,22 diene of ergot steroid 3 is a kind of new ergot steroid natural products derivative, condensation reaction can occur with thiosemicarbazides by the ketone of 7,22 diene of ergot steroid 3 and be made.In vitro Bactericidal Experiments result shows that the ketone contracting ammonia sulphur hydrazone of 7,22 diene of ergot steroid 3 has preferable anti-pathogenic activity, available for preparing antibacterials.
Description
Technical field
The present invention relates to a kind of antimicrobial compound, it is more particularly related to which ergot steroid -7,22- diene -3- ketone contracts
Ammonia sulphur hydrazone and preparation method thereof and the application in antibacterials are prepared.
Background technology
In recent years, because the abuse of antibiotic, many pathogens generate the resistance to the action of a drug, there is superbacteria, meanwhile, newly
Pathogen continuously emerges, serious threat human health.There is an urgent need to develop novel antibacterial medicine by people.To natural products guide
It is one of important method for screening new drug that thing, which carries out structural modification,.Steroid is widely present in animals and plants and microbial body
It is interior, there is diversified bioactivity.Structural modification is carried out to steroid and has resulted in a finding that many has good resist
Bacterium, the steroid derivatives of antitumor isoreactivity.Ergot steroid -7,22- diene -3- ketone is widely present in various higher fungus fructifications
In, there is antibacterial activity, anti-complement activity and platelet aggregation reinforcing agent activity.But so far, there are no on ergot steroid-
7,22- diene -3- ketone contracting ammonia sulphur hydrazones and preparation method thereof and the report of the application in antibacterials are prepared.
The content of the invention
It is an object of the invention to provide a kind of new ergot steroid derivatives, i.e. ergot steroid -7,22- diene -3- ketone contracting ammonia
Sulphur hydrazone, hereinafter referred to as compound A.
It is a further object of the present invention to provide a kind of compound A preparation method.
The further object of the present invention is to provide applications of the compound A in antibacterials are prepared.
The technical solution that the present invention uses in order to achieve the above object is as follows：
Compound A of the present invention structural formula is
The invention provides a kind of compound A preparation method, the method includes the steps of：
(1) ergot steroid -7,22- diene -3- ketone petroleum ether dissolutions are taken；
(2) thiosemicarbazides and absolute ethyl alcohol are added in reaction bulb, magnetic stir bar is inserted, loads onto spherical condensation tube, connect
Logical cooling water, being heated to pico- boiling under agitation is completely dissolved thiosemicarbazides, then adds ergot steroid -7,22- diene -3-
The petroleum ether solution of ketone, and a small amount of concentrated hydrochloric acid is added, continue agitating and heating back flow reaction until reaction is complete；
(3) reaction finishes, and reclaims most of solvent by rotary evaporation in vacuo, then adds distilled water, with isometric second
Acetoacetic ester extracts three times；
(4) combined ethyl acetate extract, washed with saturated sodium carbonate solution and the saturated common salt aqueous solution, finally used successively
Anhydrous magnesium sulfate is dried, and is filtered to remove solid, filtrate reclaims ethyl acetate by rotary evaporation in vacuo；
(5) reclaim the solid after ethyl acetate to be recrystallized with petroleum ether alcohol mixed solvent, obtain clear crystal shape chemical combination
Thing A.
Meanwhile the application present invention also offers the compound A in antibacterials are prepared.
When compound A of the present invention is used in medicine, can directly it use, or made in the form of pharmaceutical composition
With.It can be administered by spraying, oral, injection (intravenous injection, intramuscular injection) mode.
Essence for a better understanding of the present invention, the antibacterial activity in vitro of formula (A) described compound is used below
Result of the test illustrates its application in antibacterials are prepared.
1. material and method
1.1 reagent：Dimethyl sulfoxide (DMSO) (DMSO) is purple (INT) to iodonitrotetrazolium.
1.2 culture medium：M-H broth bouillons.
1.3 compound：Detection compound is compound A.
1.4 for examination pathogen：Staphylococcus aureus Staphylococcus aureu and Escherichia coli Escherichia
coli。
1.5 compound A antibacterial activity in vitro are tested
Compound A is determined in vitro to the antibacterial activity for trying pathogen by micro-dilution method, Benzylpenicillin sodium salt is positive right
According to.It is fabricated for trying bacterium bacteria suspension first.It will be inoculated in for examination pathogen in M-H broth bouillons, the quiescent culture 4h at 30 DEG C,
Bacteria suspension is obtained, 0.5 Maxwell turbidity inoculation liquid is diluted to M-H broth bouillons.Then compound sample DMSO is dissolved simultaneously
The decoction that initial concentration is 12.80 μ g/ μ L is configured to, and with syringe needle filter bacteriological filtration.Antibacterial tests are entered in sterile 96 microwell plate
OK.First add 200 μ L sterilized waters in 96 microwell plate periphery holes, remaining hole adds 100 μ L M-H broth bouillons.Then by 100 μ L
Decoction is added in the first hole of each row after bacteriological filtration, and sesquialter dilution is carried out to decoction.100 μ L inoculation liquids are finally added to each detection hole
In and without in medicine control wells.Final decoction detectable concentration scope is 0~3.20 μ g/ μ L.Culture plate 30 DEG C be incubated 18h after,
Add 20 μ L 5%INT solution per hole, continue to observe after being incubated 1h.The plate hole of pink is Growth positive.Minimum inhibitory concentration
(MIC) it is defined as the lowest concentration of drug for preventing color from being changed into pink.Experiment is in triplicate.
2. result of the test
Compound A is to staphylococcus aureus Staphylococcus aureu and Escherichia coli Escherichia coli
MIC value be respectively 1.60 μ g/ μ L and 3.20 μ g/ μ L.
Compared with prior art, the invention has the advantages that：
1. so far, there has been no on ergot steroid -7,22- diene -3- ketone contracting ammonia sulphur hydrazones and preparation method thereof and making
The report of application in standby antibacterials.
2. In vitro Bactericidal Experiments result shows, compound A can significantly inhibit the growth for examination pathogen, to golden yellow grape
Coccus Staphylococcus aureu and Escherichia coli Escherichia coli MIC value respectively for 1.60 μ g/ μ L and
3.20μg/μL.Show that compound A has preferable antibacterial activity, available for preparing antibacterials.
3. compound A of the present invention raw material ergot steroid -7,22- diene -3- ketone abundances, not only can be by artificial
Synthesis obtains, can also be isolated from higher fungus.Compound A preparation technologies are simple, both can be by spray delivery, can also
By oral and drug administration by injection, a kind of new drug candidate is provided for human treatment's bacterial infection disease.
Brief description of the drawings
Fig. 1 is the electrospray ionization mass spectrometry figure of ergot steroid -7,22- diene -3- ketone contracting ammonia sulphur hydrazones；
Fig. 2 is the hydrogen nuclear magnetic resonance wave spectrogram of ergot steroid -7,22- diene -3- ketone contracting ammonia sulphur hydrazones；
Fig. 3 is the hydrogen nuclear magnetic resonance wave spectrogram of ergot steroid -7,22- diene -3- ketone.
Embodiment
The present invention is described in detail below in conjunction with specific embodiment, herein illustrative examples and explanation of the invention
For explaining the present invention, but it is not as a limitation of the invention.
Embodiment 1
1. compound A preparation：
(1) 0.50mmol ergot steroid -7,22- diene -3- ketone is taken, with standby after 10mL petroleum ether dissolutions；
(2) 0.60mmol thiosemicarbazides and 50mL absolute ethyl alcohols are added in two mouthfuls of round-bottomed flasks, inserts magnetic stir bar,
Spherical condensation tube is loaded onto, another mouth is clogged with hollow glass plug, is connected cooling water, is heated to seething with excitement slightly under magnetic stirring
Thiosemicarbazides is completely dissolved, then adds the petroleum ether solution of ergot steroid -7,22- diene -3- ketone, and adds 5 drop concentrated hydrochloric acids,
Continue agitating and heating back flow reaction 4h, tracked with silica gel thin-layer chromatography until reacting complete；
(3) reaction is finished, and most of solvent is reclaimed by rotary evaporation in vacuo in 50 DEG C, then adds 50mL distilled water,
With the extraction of isometric ethyl acetate three times；
(4) combined ethyl acetate extract, washed with saturated sodium carbonate solution and the saturated common salt aqueous solution, finally used successively
Anhydrous magnesium sulfate is dried, and is filtered to remove solid, and filtrate reclaims ethyl acetate in 50 DEG C of rotary evaporation in vacuo；
(5) reclaim the solid after ethyl acetate to be recrystallized with petroleum ether alcohol mixed solvent, obtain clear crystal shape chemical combination
Thing A.
2. compound A Structural Identification：
Compound A molecular formula is C29H47N3S, relative molecular weight calculated value are 469.7696.Electrospray ionization mass spectrometry figure
(Fig. 1) shows its quasi-molecular ion peak respectively in 492.5 [M+Na]+(calculated value：492.7594) and 470.5 [M+H]+(calculate
Value：470.7775).
Using deuterochloroform, tetramethylsilane is internal standard for solvent, by BRUKER-400 nuclear magnetic resonance chemical analysers to changing
Compound A and raw material ergot steroid -7,22- diene -3- ketone carry out hydrogen nuclear magnetic resonance Spectrum Analysis, and as a result compound A proton magnetic is total to
Vibration wave spectrogram (Fig. 2) is in chemical shift δHIt is worth 3 alkene matter for occurring 7,22 and 23 of compound A for 5.20 (m, 3H) places
Subsignal, and in chemical shift δHValue is respectively 8.58 (br s), 7.21 (br s) and 6.16 (br s) places then than raw material ergot
The hydrogen nuclear magnetic resonance wave spectrogram (Fig. 3) of steroid -7,22- diene -3- ketone has had more 3 N-H Labile protons signals.
Composite mass spectrum and hydrogen nuclear magnetic resonance spectral information understand compound A be raw material ergot steroid -7,22- diene -3- ketone with
The product of condensation reaction, i.e. ergot steroid -7,22- diene -3- ketone contracting ammonia sulphur hydrazone occur for thiosemicarbazides.
Embodiment 2
Compound A is made by embodiment 1, excipients, system are added in the ratio of compound crystal and excipients mass ratio 1: 1
Grain tabletting.
Embodiment 3
Compound A is made by embodiment 1, excipients, system are added in the ratio of compound crystal and excipients mass ratio 1: 2
Grain tabletting.
Embodiment 4
Compound A is made by embodiment 1, excipients, system are added in the ratio of compound crystal and excipients mass ratio 1: 3
Grain tabletting.
Embodiment 5
Tablet：Compound A：50mg；Starch：50mg；Corn steep liquor：In right amount；Magnesium stearate：In right amount.
The above-described embodiments merely illustrate the principles and effects of the present invention, not for the limitation present invention.It is any ripe
Know the personage of this technology all can carry out modifications and changes under the spirit and scope without prejudice to the present invention to above-described embodiment.Cause
This, those of ordinary skill in the art is complete without departing from disclosed spirit and institute under technological thought such as
Into all equivalent modifications or change, should by the present invention claim be covered.
Claims (3)
1. a kind of new ergot steroid derivatives, ergot steroid -7,22- diene -3- ketone contracting ammonia sulphur hydrazones, its structural formula are
2. a kind of preparation method of compound described in claim 1, it is characterised in that the method includes the steps of：
(1) ergot steroid -7,22- diene -3- ketone is taken, uses petroleum ether dissolution；
(2) thiosemicarbazides and ethanol are added in reaction bulb, inserts magnetic stir bar, loads onto spherical condensation tube, connects cooling water,
Being heated to pico- boiling under agitation is completely dissolved thiosemicarbazides, then adds the oil of ergot steroid -7,22- diene -3- ketone
Ethereal solution, and add several drop concentrated hydrochloric acids and make catalyst, continue agitating and heating and be back to reaction completely；
(3) reaction finishes, and removes most of solvent by rotary evaporation in vacuo, then adds distilled water, with isometric acetic acid second
Ester extracts three times；
(4) combined ethyl acetate extract, washed successively with saturated sodium carbonate solution and the saturated common salt aqueous solution, finally with anhydrous
Magnesium sulfate is dried, and is filtered to remove solid, filtrate reclaims ethyl acetate by rotary evaporation in vacuo；
(5) reclaim the solid after ethyl acetate to be recrystallized with petroleum ether alcohol mixed solvent, obtain ergot steroid -7,22- diene -3-
Ketone contracting ammonia sulphur hydrazone is clear crystal.
3. application of the compound described in claim 1 in antibacterials are prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710809566.2A CN107746422B (en) | 2017-09-07 | 2017-09-07 | Ergosta-7, 22-diene-3-ketaminothiohydrazone, preparation method thereof and application thereof in preparation of antibacterial drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710809566.2A CN107746422B (en) | 2017-09-07 | 2017-09-07 | Ergosta-7, 22-diene-3-ketaminothiohydrazone, preparation method thereof and application thereof in preparation of antibacterial drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107746422A true CN107746422A (en) | 2018-03-02 |
| CN107746422B CN107746422B (en) | 2020-02-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710809566.2A Expired - Fee Related CN107746422B (en) | 2017-09-07 | 2017-09-07 | Ergosta-7, 22-diene-3-ketaminothiohydrazone, preparation method thereof and application thereof in preparation of antibacterial drugs |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107746423A (en) * | 2017-09-07 | 2018-03-02 | 佛山科学技术学院 | Ketoxime of 7,22 diene of ergot steroid 3 and preparation method thereof and the application in antibacterials are prepared |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1925756A (en) * | 2004-02-06 | 2007-03-07 | 福布斯梅迪泰克公司 | Method of preservation of a food prodcut and composition comprising one or more phytosterols and/or phytostanols useful for this purpose |
-
2017
- 2017-09-07 CN CN201710809566.2A patent/CN107746422B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1925756A (en) * | 2004-02-06 | 2007-03-07 | 福布斯梅迪泰克公司 | Method of preservation of a food prodcut and composition comprising one or more phytosterols and/or phytostanols useful for this purpose |
Non-Patent Citations (2)
| Title |
|---|
| SMANIA JUNIOR, ARTUR等: "Antibacterial Activity of Steroidal Compounds", 《INTERNATIONAL JOURNAL OFMEDICINAL MUSHROOMS》 * |
| 朱峰等: "南海海洋真菌2492号中的甾体成分", 《佛山科学技术学院学报(自然科学版)》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107746423A (en) * | 2017-09-07 | 2018-03-02 | 佛山科学技术学院 | Ketoxime of 7,22 diene of ergot steroid 3 and preparation method thereof and the application in antibacterials are prepared |
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| Publication number | Publication date |
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| CN107746422B (en) | 2020-02-14 |
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