CN109867637A - The preparation method of fumidil amido alcohol - Google Patents
The preparation method of fumidil amido alcohol Download PDFInfo
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- CN109867637A CN109867637A CN201711247019.6A CN201711247019A CN109867637A CN 109867637 A CN109867637 A CN 109867637A CN 201711247019 A CN201711247019 A CN 201711247019A CN 109867637 A CN109867637 A CN 109867637A
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Abstract
The invention discloses a kind of preparation methods of fumidil amido alcohol shown in Formulas I.This method includes the following steps: that (1) restores amino acid shown in Formula II, obtains compound shown in formula III；(2) under methanol solution heating condition, make compound shown in fumidil and formula III through ammonium salt synthetic reaction to get.The reaction route of preparation method of the present invention is short, and combined coefficient is high, reduces the step of isolating and purifying, can mass production.The toxicity of simultaneously synthesizing fumidil amino alcohol is low, dissolves degradation and good water solubility in nature.
Description
Technical field
The invention belongs to organic synthesis fields, and in particular to a kind of preparation method of fumidil amido alcohol.
Background technique
Fumidil is a kind of antibiotics of primary treatment microsporidiosis.Microsporidiosis main parasitic is in elder brother
In the gastrointestinal epithelial cells of worm and the skin and muscle of fish, annelid and other certain invertebrate bodies are also seen
It is interior.Crops are influenced can not be ignored by microsporidiosis.For example, microsporidiosis is not only serious to the damaging effect of honeybee
Apiculture is influenced, and influence is all produced on the even entire Agricultural Activities of crop pollination；Meanwhile the influence to fish
The health and freshwater aquiculture of fish are seriously endangered.From the point of view of the effect of external prevention and treatment microsporidiosis, fumidil class medicine
Object is the optimal selection for substituting the antifungal drugs such as metronidazole.In recent years, microsporidiosis is serious in domestic agricultural production, nearly
1/5 bee colony is influenced by microsporidiosis.Function and effect in view of fumidil and the warp in the application of part American-European countries
It tests, while lacking alternative medicine, be worth us to promote using fumidil class medical treatment microsporidiosis in China.Therefore,
It is very urgent to solve serious microsporidiosis in agricultural production to synthesize a kind of novel fumidil class medicine.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of fumidil amido alcohol, this method must can rapidly and efficiently be made
Standby fumidil amido alcohol.
The structural formula of fumidil amido alcohol of the present invention is shown in formula I:
The method of fumidil amido alcohol, includes the following steps: shown in preparation formula I provided by the invention
(1) amino acid shown in Formula II is restored, obtains compound shown in formula III；
(2) make compound shown in fumidil and formula III through ammonium salt synthetic reaction, obtain fumidil amido shown in Formulas I
Alcohol.
Wherein, reduction described in step (1) is divided into two steps: a) amino acid shown in Formula II is subjected to chloride；B) by acyl
The product of chlorination restores.
The reagent that chloride uses in the step a) is thionyl chloride, amino acid shown in the Formula II and thionyl chloride
Molar ratio be 1:1-4；The reaction of the chloride carries out in methyl alcohol, and the reaction of the chloride is first reacted at -20-10 DEG C
10-60min (concretely first in 0 DEG C of reaction 30min) is then warming up to room temperature again the reaction was continued 10-30h (concretely
24h)。
Reducing agent used by restoring in the step b) is potassium borohydride, amino acid and hydroboration shown in the Formula II
The molar ratio of potassium is 1:2-5；The reaction condition of the reduction are as follows: room temperature reaction 20-30h.
It reacts described in step (2) and carries out in a solvent, the solvent is methanol.
The molar ratio of amido polyol shown in fumidil described in step (2) and formula III is 1:1-1.5.It is described anti-
The reaction condition answered are as follows: 20-60 DEG C is stirred to react 1-3 hours, is concretely stirred to react at 50 DEG C 2 hours.
The preparation method of fumidil amido alcohol provided by the invention has the advantages that
The reaction route of preparation method of the present invention is short, and combined coefficient is high, reduces the step of isolating and purifying, can largely give birth to
It produces.The toxicity of simultaneously synthesizing fumidil amino alcohol is low, dissolves degradation and good water solubility in nature.
Detailed description of the invention
Fig. 1 is fumidil amido alcohol1H NMR spectra.
Fig. 2 is fumidil amido alcohol13C NMR spectra.
Specific embodiment
Method of the invention is illustrated below by specific embodiment, but the present invention is not limited thereto, it is all at this
Any modifications, equivalent replacements, and improvements etc. done within the spirit and principle of invention, should be included in protection model of the invention
Within enclosing.
Fumidil amido alcohol shown in embodiment 1, synthesis Formulas I
Reaction process is as follows:
(1) synthesis of compound shown in formula III
L-lysine shown in Formula II (1.0mmol) is dissolved in 0 DEG C of methanol (10ml), thionyl chloride is gradually added dropwise
(2.0mmol) keeps temperature 30min, then heats to room temperature, keeps temperature stirring for 24 hours.It is added potassium borohydride (3.0mmol),
Room temperature is kept to continue stirring for 24 hours.After completion of the reaction, water phase is washed with ethyl acetate, retains water phase, the pH value of water phase is adjusted to
Alkaline (pH > 10) then add ethyl acetate with separatory funnel and carry out washing 3 times to water phase, anhydrous magnesium sulfate drying is added,
After being concentrated using Rotary Evaporators, crude samples are obtained.It is final to place ventilation, dry to obtain compound shown in formula III, yield is
70%.
(2) synthesis of compound shown in Formulas I:
By amido polyol (1.2mmol) shown in fumidil (1.0mmol) and formula III according to molar ratio 1:1's
Amount is added in round-bottomed flask, is placed in 50 DEG C of water-bath, methanol solution (20ml) is then gradually added into, until white powder
End is gradually dissolved, and keeps stirring 2 hours under bath temperature.Then obtained reaction mixture is evaporated in Rotary Evaporators,
Obtain the alcoholic compound of fumidil amido shown in Formulas I.After being concentrated using Rotary Evaporators, crude samples are obtained, chromatograph (stone by column
Oily ether: ethyl acetate=10:1, volume ratio) purifying obtain compound shown in Formulas I.The gross production rate of two-step reaction is 50%.
Fumidil amido alcoholic compound shown in Formulas I manufactured in the present embodiment1H NMR spectra as shown in Figure 1,13C NMR
Spectrogram is really target compound as shown in Fig. 2, the structure of compound prepared it can be seen from 2 spectrograms is correct.
Claims (7)
1. the method for fumidil amido alcohol shown in preparation formula I, includes the following steps:
(1) amino acid shown in Formula II is restored, obtains compound shown in formula III；
(2) make compound shown in fumidil and formula III through ammonium salt synthetic reaction, obtain the alcohol of fumidil amido shown in Formulas I.
2. according to the method described in claim 1, it is characterized by: the reduction is divided into two steps in the step (1): a) will
Amino acid shown in Formula II carries out chloride；B) product of chloride is restored.
3. according to the method described in claim 2, it is characterized by: in the step a), reagent that the chloride uses for
Thionyl chloride, the molar ratio of amino acid and thionyl chloride shown in the Formula II are 1:1-4；The reaction of the chloride is in methanol
Then middle progress, the reaction of the chloride are warming up to room temperature again the reaction was continued 10- first in -20-10 DEG C of reaction 10-60min
30h。
4. according to the method described in claim 2, it is characterized by: in the step b), reducing agent used by the reduction
For potassium borohydride, the molar ratio of amino acid shown in the Formula II and potassium borohydride is 1:2-5；The reaction condition of the reduction
Are as follows: room temperature reaction 20-30h.
5. method according to any one of claims 1-4, it is characterised in that: in the step (2), the reaction is in solvent
Middle progress, the solvent are methanol.
6. any method in -5 according to claim 1, it is characterised in that: in the step (2), the fumidil with
The molar ratio of amido polyol shown in formula III is 1:1-1.5.
7. method according to claim 1 to 6, it is characterised in that: in the step (2), the reaction it is anti-
Answer condition are as follows: 20-60 DEG C is stirred to react 1-3 hours.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109867640A (en) * | 2017-12-01 | 2019-06-11 | 中国农业科学院农业质量标准与检测技术研究所 | A kind of preparation method of fumidil amido alcohol |
| CN109867639A (en) * | 2017-12-01 | 2019-06-11 | 中国农业科学院农业质量标准与检测技术研究所 | The method for preparing fumidil amido alcohol |
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| CN106831662A (en) * | 2016-12-29 | 2017-06-13 | 中国农业科学院蜜蜂研究所 | A kind of amido polyol is for fumidil and its synthetic method and application |
| CN109867640A (en) * | 2017-12-01 | 2019-06-11 | 中国农业科学院农业质量标准与检测技术研究所 | A kind of preparation method of fumidil amido alcohol |
| CN109867639A (en) * | 2017-12-01 | 2019-06-11 | 中国农业科学院农业质量标准与检测技术研究所 | The method for preparing fumidil amido alcohol |
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| CN106831662A (en) * | 2016-12-29 | 2017-06-13 | 中国农业科学院蜜蜂研究所 | A kind of amido polyol is for fumidil and its synthetic method and application |
| CN109867640A (en) * | 2017-12-01 | 2019-06-11 | 中国农业科学院农业质量标准与检测技术研究所 | A kind of preparation method of fumidil amido alcohol |
| CN109867639A (en) * | 2017-12-01 | 2019-06-11 | 中国农业科学院农业质量标准与检测技术研究所 | The method for preparing fumidil amido alcohol |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109867640A (en) * | 2017-12-01 | 2019-06-11 | 中国农业科学院农业质量标准与检测技术研究所 | A kind of preparation method of fumidil amido alcohol |
| CN109867639A (en) * | 2017-12-01 | 2019-06-11 | 中国农业科学院农业质量标准与检测技术研究所 | The method for preparing fumidil amido alcohol |
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