CN103058903B - Synthesis method for allicin derivative - Google Patents
Synthesis method for allicin derivative Download PDFInfo
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- CN103058903B CN103058903B CN201110324112.9A CN201110324112A CN103058903B CN 103058903 B CN103058903 B CN 103058903B CN 201110324112 A CN201110324112 A CN 201110324112A CN 103058903 B CN103058903 B CN 103058903B
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- garlicin
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- analog derivative
- hydrogen peroxide
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Abstract
The invention discloses a synthesis method for an allicin derivative. The allicin derivative has the structural general formula as the specification. The synthesis method comprises the following step of enabling R1-S-S-R2 as a raw material to react with hydrogen peroxide in a solvent by taking proline as a catalyst, wherein R1 and R2 are same or different and are C1-C4 alkanes or C2-C4 alkylenes. The synthesis method disclosed by the invention has the advantages of mild reaction condition, simplicity and convenience in operation, higher reaction yield, cleanness, environment friendliness and the like, meets the requirement of industrial production, and provides feasibility for wide popularization and application of the allicin derivative.
Description
Technical field
The synthetic method that the present invention relates to garlicin analog derivative, belongs to technical field of organic synthesis.
Background technology
Garlic (Alliiridum) is the traditional food and medicament dual-purpose plant of China, and garlicin is from garlic bulb, to extract the separated effective constituent obtaining, and structural formula is CH
2=CH-CH
2-S-S-S-CH
2-CH=CH
2, chemical name is Diallytrisin.Scientific research result shows, garlicin has many-sided medical treatment and health-care effect, it has inhibition and killing action in various degree to the pathogenic micro-organisms such as various bacteria, virus, fungi and tumour etc., in addition, it also have hypotensive, reducing blood-fat, hypoglycemic, improve immunity of organisms and the pharmacologically active such as anti-oxidant.At present, garlicin is used mainly as antibacterials clinically, has the reputation of natural Broad spectrum antibiotics, is applicable to bacterium and infects and deep fungal infection.But there is the shortcomings such as the strong and poor stability of pungency in garlicin, it is applied and be very limited.
At present, Chinese scholars mainly reduces the pungency of garlicin by physical methods such as entrapping method, microwave ultrasound methods, but these methods can not tackle the problem at its root, and likely reduces the pharmacologically active of garlicin.Wherein, the cyclodextrin encapsulated method of D mono-is to generally acknowledge good method, but also has the problems such as encapsulation rate is not high, effect is undesirable, cost is higher.Research shows: the garlicin analog derivative with following general structure
not only stable in properties, free from extraneous odour, and sterilization effect is good, can fundamentally solve the shortcomings (J.Am.Chem.Soc., 1947,69,1710～1713.) such as the strong and poor stability of pungency that garlicin exists.But, in prior art about preparation method's existence condition of above-mentioned garlicin analog derivative is harsh, reagent is expensive, complex steps, series of problems (J.Am.Chem.Soc., 1949 such as yield is low and environmental pollution is large, 71,3565～3566 and J.Am.Chem.Soc., 1997,119,9309～9310 and J.Org.Chem., 1978,43 (13), 2728～2730), be not suitable for suitability for industrialized production, so that affected the wide popularization and application of this analog derivative.
Summary of the invention
For the existing the problems referred to above of prior art and defect, the invention provides that a kind of preparation condition is gentle, yield is higher, simple to operate and the synthetic method of the above-mentioned garlicin analog derivative of clean environment firendly.
For achieving the above object, the technical solution used in the present invention is as follows:
A synthetic method for garlicin analog derivative, described garlicin analog derivative has following general structure:
its synthetic method comprise the steps: with
for raw material, proline(Pro) is catalyzer, in solvent with hydroperoxidation; Wherein: R
1with R
2identical or different, be C
1-C
4alkyl or C
2-C
4alkylene.
The synthetic method of described garlicin analog derivative, can also comprise the steps: with
for raw material, proline(Pro) is catalyzer, under oxygenant effect, in solvent with hydroperoxidation; Wherein: R
1with R
2identical or different, be C
1-C
4alkyl or C
2-C
4alkylene.
Described R
1with R
2be preferably identically, and be all preferably methyl, ethyl, propyl group, butyl, sec.-propyl or allyl group.
Described
be recommended as 1: 1 with the mol ratio of hydrogen peroxide～1: 5; Be preferably 1: 1～1: 3.
Described temperature of reaction is recommended as 0～60 ℃; Be preferably 0～40 ℃.
Described solvent is recommended as water, ethyl acetate, tetrahydrofuran (THF), methyltetrahydrofuran, t-butyl methyl ether, acetonitrile, methylene dichloride or 1,2-ethylene dichloride; Be preferably water, t-butyl methyl ether, acetonitrile or 1,2-ethylene dichloride.
Described oxygenant is recommended as the vitriol oil, concentrated nitric acid, chlorine, clorox, peroxy tert-butyl alcohol or metachloroperbenzoic acid; Be preferably concentrated nitric acid, chlorine, peroxy tert-butyl alcohol or metachloroperbenzoic acid.
Described oxygenant and the mol ratio of hydrogen peroxide be recommended as 0.1: 1～and 0.8: 1; Be preferably 0.2: 1～0.5: 1.
Compared with prior art, synthetic method of the present invention has reaction conditions gentleness, easy and simple to handle, reaction yield is higher and the advantage such as clean environment firendly, is applicable to industrialization production requirements, for the wide popularization and application of described garlicin analog derivative provides feasibility.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail and completely.
Embodiment 1: methyl sulfo--sulfinic acid methyl esters
preparation
Methyl disulfide (20g) and L-PROLINE (2g) are dissolved in acetonitrile (10ml), at 0 ℃, drip wherein hydrogen peroxide (30%, 40g); Stir, be naturally warmed up to 25 ℃, after question response is complete, at 20 ℃, acetonitrile is removed in decompression; Add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; Concentrating under reduced pressure at 20 ℃, removes solvent, and the faint yellow oily product obtaining, is methyl sulfo--sulfinic acid methyl esters 18.7g, molar yield 80%, HPLC purity > 90%.
Embodiment 2: methyl thiosulfonic acid methyl esters
preparation
Methyl disulfide (40g) and L-PROLINE (4g) are dissolved in methyltetrahydrofuran (10ml), at 10 ℃, drip wherein hydrogen peroxide (30%, 150g); Stir, be naturally warmed up to 30 ℃, after question response is complete, at 20 ℃, methyltetrahydrofuran is removed in decompression; Add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; Concentrating under reduced pressure at 20 ℃, removes solvent, and the faint yellow oily product obtaining, is methyl thiosulfonic acid methyl esters 46g, molar yield 85%, HPLC purity > 90%.
Embodiment 3: ethylenebis dithiocarbamate-sulfinic acid ethyl ester
preparation
Diethyl two sulphur (100g) and L-PROLINE (5g) are dissolved in 1,2-ethylene dichloride (40ml), at 10 ℃, drip wherein hydrogen peroxide (30%, 160g); Stir, be warmed up to 40 ℃, after question response is complete, add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; Concentrating under reduced pressure at 20 ℃, removes solvent, and the faint yellow oily product obtaining, is ethylenebis dithiocarbamate-sulfinic acid ethyl ester 90g, molar yield 80%, HPLC purity > 90%.
Embodiment 4: O-Ethyl ethanesulfonothioate
preparation
Diethyl two sulphur (10g) and L-PROLINE (1g) are dissolved in methyl tertiary butyl ether (10ml), at 10 ℃, drip wherein hydrogen peroxide (30%, 22g); Under stirring, add peroxy tert-butyl alcohol (6g) again, be slowly warmed up to 60 ℃, after question response is complete, at 20 ℃, concentrating under reduced pressure is removed solvent; Add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; At 20 ℃, concentrating under reduced pressure is removed solvent, and the faint yellow oily product obtaining, is O-Ethyl ethanesulfonothioate 10g, molar yield 78%, HPLC purity > 90%.
Embodiment 5: isopropylthio-sulfinic acid isopropyl ester
preparation
Sec.-propyl two sulphur (50g) and L-PROLINE (1g) are dissolved in ethyl acetate (15ml), at 10 ℃, drip wherein hydrogen peroxide (30%, 76g); Stir, be warmed up to 40 ℃, after question response is complete, add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; At 20 ℃, concentrating under reduced pressure is removed solvent, and the faint yellow oily product obtaining, is isopropylthio-sulfinic acid isopropyl ester 45g, molar yield 82%, HPLC purity > 90%.
Embodiment 6: isopropylthio sulfonic acid isopropyl ester
preparation
Sec.-propyl two sulphur (50g) and L-PROLINE (1g) are dissolved in acetonitrile (15ml), at 10 ℃, drip wherein hydrogen peroxide (30%, 160g); Under stirring, add concentrated nitric acid (9g) again, be slowly warmed up to 50 ℃, after question response is complete, at 20 ℃, concentrating under reduced pressure is removed solvent; Add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; At 20 ℃, concentrating under reduced pressure is removed solvent, and the faint yellow oily product obtaining, is isopropylthio sulfonic acid isopropyl ester 47g, molar yield 78%, HPLC purity > 90%.
Embodiment 7: allyl group thiosulfonic acid allyl ester
preparation
By in diallyl disulfide (10g) and L-PROLINE (1g) water-soluble (10ml), at 10 ℃, drip wherein hydrogen peroxide (30%, 22g), stir, be warmed up to 50 ℃, after question response is complete, add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; Concentrating under reduced pressure at 20 ℃, removes solvent, and the faint yellow oily product obtaining, is allyl group thiosulfonic acid allyl ester 10g, molar yield 82%, HPLC purity > 90%.
Embodiment 8: allyl sulfide is for-sulfinic acid allyl ester
preparation
Diallyl disulfide (10g) and L-PROLINE (1g) are dissolved in methyltetrahydrofuran (10ml), at 20 ℃, drip wherein hydrogen peroxide (30%, 10g), stir, be warmed up to 40 ℃, after question response is complete, add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; At 20 ℃, concentrating under reduced pressure is removed solvent, obtains faint yellow oily product product, is allyl sulfide for-sulfinic acid allyl ester 9g, molar yield 80%, HPLC purity > 90%.
Embodiment 9: methyl sulfo--sulfinic acid allyl ester
preparation
Methacrylic two sulphur (20g) and L-PROLINE (1g) are dissolved in 1,2-ethylene dichloride (10ml), at 10 ℃, drip wherein hydrogen peroxide (30%, 43g); Stir, be warmed up to 40 ℃, after question response is complete, add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; At 20 ℃, concentrating under reduced pressure is removed solvent, and the faint yellow oily product obtaining, is methyl sulfo--sulfinic acid allyl ester 19g, molar yield 85%, HPLC purity > 90%.
Embodiment 10: methyl thiosulfonic acid ethyl ester
preparation
Methylethyl two sulphur (20g) and L-PROLINE (1g) are dissolved in acetonitrile (10ml), at 10 ℃, drip wherein hydrogen peroxide (30%, 86g); Under stirring, add clorox (46g) again, be slowly warmed up to 60 ℃, after question response is complete, at 20 ℃, concentrating under reduced pressure is removed solvent; Add dichloromethane extraction layering, collected organic layer, with after saturated common salt water washing, with anhydrous sodium sulfate drying; Concentrating under reduced pressure at 20 ℃, removes solvent, and the faint yellow oily product obtaining, is methyl thiosulfonic acid ethyl ester 19g, molar yield 75%, HPLC purity > 90%.
In sum, adopt that the synthetic garlicin analog derivative of the inventive method has reaction conditions gentleness, easy and simple to handle, reaction yield is higher and the advantage such as clean environment firendly, be applicable to industrialization production requirements.
Be necessary to be pointed out that at this: above-described embodiment is only used to further illustrate the present invention; can not be interpreted as limiting the scope of the invention, some nonessential improvement that those skilled in the art's foregoing according to the present invention is made and adjustment all belong to protection scope of the present invention.
Claims (6)
1. a synthetic method for garlicin analog derivative, described garlicin analog derivative has following general structure:
it is characterized in that, described synthetic method comprise the steps: with
for raw material, proline(Pro) is catalyzer, under oxygenant effect, in solvent with hydroperoxidation; Wherein: R
1with R
2difference, described R
1for methyl, R
2for ethyl or allyl group;
Described
with the mol ratio of hydrogen peroxide be 1:1～1:5;
Described oxygenant and the mol ratio of hydrogen peroxide are 0.1:1～0.8:1;
Described temperature of reaction is 0～60 ℃;
Described solvent is water, ethyl acetate, tetrahydrofuran (THF), methyltetrahydrofuran, t-butyl methyl ether, acetonitrile, methylene dichloride or 1,2-ethylene dichloride;
Described oxygenant is the vitriol oil, concentrated nitric acid, chlorine, clorox, peroxy tert-butyl alcohol or metachloroperbenzoic acid.
2. the synthetic method of garlicin analog derivative according to claim 1, is characterized in that: described
with the mol ratio of hydrogen peroxide be 1:1～1:3.
3. the synthetic method of garlicin analog derivative according to claim 1, is characterized in that: described temperature of reaction is 0～40 ℃.
4. the synthetic method of garlicin analog derivative according to claim 1, is characterized in that: described solvent is water, t-butyl methyl ether, acetonitrile or 1,2-ethylene dichloride.
5. the synthetic method of garlicin analog derivative according to claim 1, is characterized in that: described oxygenant is concentrated nitric acid, chlorine, peroxy tert-butyl alcohol or metachloroperbenzoic acid.
6. the synthetic method of garlicin analog derivative according to claim 1, is characterized in that: described oxygenant and the mol ratio of hydrogen peroxide are 0.2:1～0.5:1.
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|---|---|---|---|
| CN201110324112.9A CN103058903B (en) | 2011-10-21 | 2011-10-21 | Synthesis method for allicin derivative |
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Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4992578A (en) * | 1990-03-09 | 1991-02-12 | Atochem North America, Inc. | Preparation of alkyl alkanethiolsulfonates |
| AU2002235749A1 (en) * | 2000-12-15 | 2002-06-24 | Bayer Aktiengesellschaft | Thiosulphonic s-esters as material protective agent |
| CN102807517A (en) * | 2011-06-02 | 2012-12-05 | 上海科材生物科技有限公司 | Synthesis of garlicin derivatives and preparation method for medical ultrasonic couplant with efficient disinfection function using garlicin derivatives |
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Non-Patent Citations (1)
| Title |
|---|
| K.Rajender Reddy等.L-Proline-H2O2：A New Chemoselective Approach for Oxidation of Sulfides to Sulfoxides.《Synthetic Communications》.2006,第36卷 * |
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Effective date of registration: 20211116 Address after: 201605 Building 2, No. 309, Haohai Road, Xinbang Town, Songjiang District, Shanghai Patentee after: Shanghai Laishen Biotechnology Co., Ltd Address before: 200032 No. 354, Fenglin Road, Xuhui District, Shanghai Patentee before: Shanghai Institute of organic chemistry, Chinese Academy of Sciences |