CN103113253A - Alcohol amine derivative of unsaturated fatty acid and preparation method and application thereof - Google Patents

Alcohol amine derivative of unsaturated fatty acid and preparation method and application thereof Download PDF

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CN103113253A
CN103113253A CN201310032202XA CN201310032202A CN103113253A CN 103113253 A CN103113253 A CN 103113253A CN 201310032202X A CN201310032202X A CN 201310032202XA CN 201310032202 A CN201310032202 A CN 201310032202A CN 103113253 A CN103113253 A CN 103113253A
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fatty acid
acid
preparation
propanolamine
sulfonamide derivatives
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方华
谢全灵
张怡评
晋文慧
洪专
易瑞灶
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Third Institute of Oceanography SOA
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Abstract

The invention discloses an alcohol amine derivative of unsaturated fatty acid and a preparation method and an application thereof, and relates to a compound. The derivative is abbreviated for an ethanolamine compound of unsaturated fatty acid or a propanolamine compound of unsaturated fatty acid. The derivative comprises ethanolamine linoleate, ethanolamine of timnodonic acid, ethanolamine of docosahexenoic acid, propanolamine oleate, propanolamine linoleate, propanolamine of timnodonic acid, propanolamine of docosahexenoic acid and the like. The preparation method comprises the following steps of: adding pre-hydrated organic solvent, unsaturated fatty acid, amine and molecular sieve into a three-opening bottle; then, adding immobilized lipase Novozym435; heating in a water bath for dehydrating and synthesizing reaction; then, filtering solids, performing decompressing concentration for the filtrate, and adding water and dichloromethane; after extraction, drying and filtering with anhydrous MgSO4 for organic phase, performing decompressing concentration to obtain a coarse product, and performing column chromatography to obtain the product. The alcohol amine derivative of unsaturated fatty acid can be applied to preparing weight-reducing products.

Description

A kind of unsaturated polyol fatty acid sulfonamide derivatives and preparation method thereof and application
Technical field
The present invention relates to a kind of compound, especially relate to a kind of preparation method and application of unsaturated polyol fatty acid sulfonamide derivatives, and this kind compound shows the effect of obvious reduction mouse appetite, reduction Mouse Weight and reduction blood fat in the activity experiment of high blood lipid model mouse.
Background technology
Along with the improvement of socioeconomic development, material life condition and the change of mode of life, incidence of obesity is constantly rising year by year, and rejuvenation situation occurs.Report of survey according to various countries' obesity of World Health Organization issue shows, the world today has at least 1,600,000,000 people overweight or fat.The fat Nutrition and Metabolism disease that is caused by obesity such as diabetes, obesity, hypertension, type ii diabetes, abnormal lipidemia, coronary heart disease, atherosclerosis, osteoarthritis, colorectal carcinoma have become a class disease ([1] Xia Yamu of serious threat human health, Wang Wei, Wang Qi, the bioactive progress of ocean polyunsaturated fatty acid, chemistry and biotechnology, 2008,25:13-16; [2] Riva S., Biocatalytic modification ofnatural products, Curr Opinionin Chem Bio2001,5:106).In recent years research finds, unsaturated polyol fatty acid amine (PUFA) has unique effect aspect fat alleviating, and side effect is little, potential huge application prospect.
Unsaturated polyol fatty acid amine is the derivative of fatty acid that extensively is present in animal body, and they are the important biologically active substances of a class, and the structural formula of this compounds is:
Figure BDA00002782046300011
Multiple unsaturated polyol fatty acid amine (PUFA) also can be used as signaling molecule and participates in the ingestion of food regulate process, therefore be used as satiety signals.Ethanolamine oleate OEA is a kind of endogenous grease, and is very high to the avidity of peroxysome activated receptor α (PeroxisomeProliferator-activated Receptor alpha, PPAR α), and less to the side effect of human body.Except the OEA that finds prototype, other Marlamid compound and homologue find that also identical pharmacologically active is arranged ([3] D Pi Nuomeili, FR De Fengsaika reduces body fat and method, compound and the composition of regulating fatty acid metabolism, Chinese patent CN1523982), as DHA thanomin (DHEA), can reduce fat with them, treatment is fat, comprises losing weight, lower appetite or food intake, and regulate Fatty Acid Oxidation.They are expected to bringing into play positive effect in the future aspect mankind's Bariatric.
Summary of the invention
The first purpose of the present invention is to provide a kind of unsaturated polyol fatty acid sulfonamide derivatives.
The second purpose of the present invention is to provide the preparation method of a kind of mild condition, easy to operate unsaturated polyol fatty acid sulfonamide derivatives.
The 3rd purpose of the present invention is to provide the application of unsaturated polyol fatty acid sulfonamide derivatives in the preparation weight reduction product.
Described unsaturated polyol fatty acid sulfonamide derivatives is the abbreviation of unsaturated fatty acids thanomin or unsaturated fatty acids Propanolamine compound, and the general structure of described unsaturated polyol fatty acid sulfonamide derivatives is as follows:
Figure BDA00002782046300021
Wherein, n=0,3,6; M=1,2,5,6; L=2,3,7; K=2,3.
Described unsaturated polyol fatty acid sulfonamide derivatives comprises linolic acid thanomin (2a), timnodonic acid thanomin (2b), docosahexenoic acid thanomin (2c), oleic acid Propanolamine (2d), linolic acid Propanolamine (2e), timnodonic acid Propanolamine (2f), docosahexenoic acid Propanolamine (2g) etc.
The preparation method of described unsaturated polyol fatty acid sulfonamide derivatives comprises the following steps:
1) under the condition of nitrogen protection, add in tool plug ground there-necked flask predrainage organic solvent, unsaturated fatty acids, amine,
Figure BDA00002782046300022
Molecular sieve, then add immobilized lipase Novozym435, heat the building-up reactions of dewatering in water-bath, get reaction solution;
In step 1), the organic solvent of described predrainage, unsaturated fatty acids, amine,
Figure BDA00002782046300023
The proportioning of molecular sieve can be: the organic solvent 20mL of predrainage: unsaturated fatty acids 10mmol: amine (10～15) mmol:
Figure BDA00002782046300024
Molecular sieve (2～5) g, the add-on of described immobilized lipase Novozym435 can be 0.5～1g; Described organic solvent can be selected from a kind of in methylene dichloride, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, glycol dimethyl ether etc.; Described unsaturated fatty acids can be selected from a kind of in oleic acid, linolic acid, timnodonic acid, docosahexenoic acid etc.; Described amine can be selected from a kind of in thanomin, Propanolamine etc.; Described unsaturated fatty acids and amine are 1 in molar ratio: (1～1.5); The temperature of described water bath with thermostatic control can be 40～60 ℃; The described reaction times can be 10～36h.
2) the reaction solution elimination solids that step 1) is obtained, filtrate decompression is concentrated, adds entry and methylene dichloride, after extraction, the anhydrous MgSO of organic phase 4Drying is filtered, and concentrating under reduced pressure obtains crude product, and the normal pressure column chromatography namely gets product.
In step 2) in, the reaction solution elimination solids that described step 1) obtains can adopt sand core funnel elimination solids; Described extraction can extract 2～3 times; Described column chromatography, its column packing can be selected from silica gel, AgNO 3, CuCl 2Deng at least a, as adopting silica gel and AgNO 3, or CuCl 2And silica gel, in mass ratio, AgNO 3: silica gel=1: (2～10), CuCl 2: silica gel=1: 300～400 order silica gel can be adopted in (2～5), described silica gel.
Described unsaturated polyol fatty acid sulfonamide derivatives can be used in the preparation weight reduction product.
With the unsaturated polyol fatty acid sulfonamide derivatives of method preparation of the present invention, it is compound a kind of novel structure and that have obvious reduction mouse appetite and reduction Mouse Weight.By the synthetic different saturation fatty acid ethanolamide amine of this preparation method and different saturation lipid acid Propanolamine, with Triton WR-1339 inducing mouse acute hyperlipemia, simultaneously, utilize the unsaturated polyol fatty acid sulfonamide derivatives mouse to be carried out the treatment of effect for reducing fat.Experimental result shows, the unsaturated polyol fatty acid sulfonamide derivatives can reduce the content of model mice triglyceride in serum to some extent.The advantages such as therefore the unsaturated polyol fatty acid sulfonamide derivatives is a kind of new type functional goods that possess the depress appetite function, has a bioavailability high, and security is good this shows, the application that the unsaturated polyol fatty acid sulfonamide derivatives can be in preparing weight reduction product.
Description of drawings
Fig. 1 is the ESI mass spectrum of compound 2c.In Fig. 1, X-coordinate is mass-to-charge ratio (m/z).
Fig. 2 is compound 2c's 1H NMR hydrogen spectrogram.In Fig. 2, X-coordinate is chemical shift (ppm).
Fig. 3 is compound 2c's 13C NMR carbon spectrogram.In Fig. 3, X-coordinate is chemical shift (ppm).
Fig. 4 is the DEPT spectrogram of compound 2c.In Fig. 4, X-coordinate is chemical shift (ppm).
Fig. 5 is the HMBC spectrogram of compound 2c.In Fig. 5, X-coordinate is chemical shift (ppm), and ordinate zou is chemical shift (ppm).
Fig. 6 is the IR infrared spectrum of compound 2c.In Fig. 6, X-coordinate is wave number (cm -1), ordinate zou is transmitance (%).
Fig. 7 is that the unsaturated polyol fatty acid sulfonamide derivatives is on the impact of mice serum triglyceride content.In Fig. 7, X-coordinate is compound, and ordinate zou is the content (mmol/L) of triglyceride; Mark ● be the blank group, ■ is model group, ▲ be the administration group.
Fig. 8 is Normal group, hyperlipidemia model group and administration (2c) group weight of mice curve.In Fig. 8, X-coordinate for raise number of days (my god), ordinate zou is Mouse Weight (g); Mark ◆ be Normal group, ■ are the hyperlipidemia model group, ▲ be administration (2c) group.
Embodiment
The present invention is further illustrated in connection with accompanying drawing for following examples.
Embodiment 1: preparation linolic acid ethanolamine compound (2a), and the structural formula of compound (2a) is:
Figure BDA00002782046300031
The synthesis step of compound is as follows:
Under the condition of nitrogen protection, add methylene dichloride, 10mmol linolic acid, 12mmol thanomin, the 3.0g of 20mL predrainage in 50mL tool plug ground there-necked flask
Figure BDA00002782046300041
Molecular sieve, then add 0.5g immobilized lipase Novozym435, heated and stirred reaction 24h in 45 ℃ of waters bath with thermostatic control.With the reaction solution elimination solids that obtains, filtrate decompression is concentrated, adds 80mL water, dichloromethane extraction 3 times, the anhydrous MgSO of organic phase 4Dried overnight is filtered, and concentrating under reduced pressure obtains crude product, and the normal pressure column chromatography namely gets product.
Main physical and the chemical property of compound (2a) are as follows:
1H?NMR(400MHz,CDCl 3,δ:ppm):6.20(br,1H,NH),5.38-5.34(m,4H,2-CH=CH-),3.72(t,J=6Hz,2H,C H 2OH),3.48-3.41(m,2H,NHC H 2),2.97-2.72(m,2H,CH 2),2.22-1.19(m,2H,CH 2),2.06-2.00(m,3H,CH 2,OH),1.68-1.59(m,2H,CH 2),1.31-1.00(m,16H,8CH 2),0.96-0.89(m,3H,CH 3);
13C NMR (100MHz, CDCl 3, δ: ppm): 174.5 (C=O), 130.2,130.0,128.0,127.9 (olefinic carbons), 62.4 ( CH 2OH), 42.4 (NH CH 2), 36.7,31.9,31.5,29.8,29.7,29.6,29.5,29.3,29.2,29.1,27.2,25.7,25.6,22.7,22.6,14.1 ( CH 3);
IR (KBr) ν (cm -1): 3303 (N-H), 2926 (HC=CH), 1734 (C=O), 1645,1558,1459,1219,1061,721 (cis-form olefin);
MS?m/z[M+H] +324,[M+Na] +346,291,223;
HRMS (TOF-MS) exact mass calcd for[C 20H 37NO 2+ Na] +Theoretical value 346.2716, measured value 346.2708.
Embodiment 2: preparation timnodonic acid ethanolamine compound (2b), and the structural formula of compound (2b) is:
Figure BDA00002782046300042
The synthesis step of compound is as follows:
Under the condition of nitrogen protection, add methylene dichloride, 10mmol timnodonic acid, 12mmol thanomin, the 3.0g of 20mL predrainage in 50mL tool plug ground there-necked flask
Figure BDA00002782046300043
Molecular sieve, then add 0.5g immobilized lipase Novozym435, heated and stirred reaction 36h in 45 ℃ of waters bath with thermostatic control.With the reaction solution elimination solids that obtains, filtrate decompression is concentrated, adds 80mL water, dichloromethane extraction 3 times, the anhydrous MgSO of organic phase 4Dried overnight is filtered, and concentrating under reduced pressure obtains crude product, and the normal pressure column chromatography namely gets product.
Main physical and the chemical property of compound (2b) are as follows:
1H?NMR(400MHz,CDCl 3,δ:ppm):6.06(br,1H,NH),5.59-5.29(m,10H,5CH=CH-),3.71(d,J=6Hz,2H,C H 2OH),3.43(d,J=6Hz,2H,NHC H 2),2.96-2.2.69(m,8H,4CH 2),2.30-2.21(m,2H,CH 2),2.16-2.2.07(m,4H,2CH 2),1.78-1.74(m,2H,CH 2),1.32-1.27(br,1H,OH),0.99-0.95(m,3H,CH 3);
13C NMR (100MHz, CDCl 3, δ: ppm): 174.2 (C=O), 132.1,129.0,128.8,128.6,128.3,128.2,128.1,127.9,127.0 (olefinic carbons), 62.4 ( CH 2OH), 42.4 (NH CH 2), 36.3,35.9,26.6,25.6,25.5,25.4,23.4,20.6,14.3 ( CH 3);
IR (KBr) ν (cm -1): 3296 (N-H), 3011 (HC=CH), 1646 (C=O), 1547,1443,1265,1066,921,706 (cis-form olefin);
MS?m/z[M+H] +346,[M+Na] +368,285,320;
HRMS (TOF-MS) exact mass calcd for[C 22H 35NO 2+ Na] +Theoretical value 368.2560, measured value 368.2563.
Embodiment 3: preparation docosahexenoic acid ethanolamine compound (2c), and the structural formula of compound (2c) is:
Figure BDA00002782046300051
The synthesis step of compound is as follows:
Under the condition of nitrogen protection, add methylene dichloride, 10mmol docosahexenoic acid, 12mmol thanomin, the 3.0g of 20mL predrainage in 50mL tool plug ground there-necked flask Molecular sieve, then add 0.5g immobilized lipase Novozym435, heated and stirred reaction 36h in 45 ℃ of waters bath with thermostatic control.With the reaction solution elimination solids that obtains, filtrate decompression is concentrated, adds 80mL water, dichloromethane extraction 3 times, the anhydrous MgSO of organic phase 4Dried overnight is filtered, and concentrating under reduced pressure obtains crude product, and the normal pressure column chromatography namely gets product.
Main physical and the chemical property of compound (2c) are as follows:
1H NMR (400MHz, CDCl 3, δ: ppm): 6.12 (br, 1H, NH), 5.43-5.32 (m, 12H, 6CH=CH-), 3.71 (t, J=4Hz, 2H, C H 2OH), 3.42 (t, J=4Hz, 2H, NHC H 2), 2.85-2.80 (m, 10H, 5CH 2), 2.43-2.39 (m, 2H, CH 2), 2.29-2.25 (m, 2H, CH 2), 2.10-2.06 (m, 2H, CH 2), 1.42-1.28 (br, 1H, OH), 0.99-0.89 (m, 3H, CH 3), (as shown in Figure 2, the hydrogen of compound 2c spectrum has reasonable ownership);
13C NMR (100MHz, CDCl 3, δ: ppm): 173.7 (C=O), 132.1,129.5,128.6,128.3,128.3,128.2,128.1,128.0,127.9,127.0 (olefinic carbons), 62.4 ( CH 2OH), 42.5 (NH CH 2), 36.3,25.6,25.6,25.5,23.4,20.6,14.3 ( CH 3), (as shown in Figure 3, it is the DEPT spectrogram that the carbon of compound 2c spectrum has reasonable ownership, Fig. 4, and the peak is to representing that up this carbon is secondary carbon CH 2, the peak is to representing that down this carbon is primary carbon CH 3Or quaternary carbon CH, Fig. 5 is the carbon-hydrogen remote couplings figure of compound 2c);
IR (KBr) ν (cm -1): 3304 (N-H), 3012 (HC=CH), 1647 (C=O), 1549,1441,1269,1067,920,708 (cis-form olefin), (as shown in Figure 6, the infrared absorption spectrum of compound 2c has reasonable ownership);
MS?m/z[M+H] +372,[M+Na] +394,229,301;
HRMS (TOF-MS) exact mass calcd for[C 24H 37NO 2+ Na] +Theoretical value 394.2716, measured value 394.2718.
Embodiment 4: preparation oleic acid Propanolamine compound (2d), and the structural formula of compound (2d) is:
Figure BDA00002782046300061
The synthesis step of compound is as follows:
Under the condition of nitrogen protection, add Isosorbide-5-Nitrae-dioxane, 10mmol oleic acid, 12mmol Propanolamine, the 3.0g of 20mL predrainage in 50mL tool plug ground there-necked flask
Figure BDA00002782046300062
Molecular sieve, then add 0.5g immobilized lipase Novozym435, heated and stirred reaction 24h in 60 ℃ of waters bath with thermostatic control.With the reaction solution elimination solids that obtains, filtrate decompression is concentrated, adds 80mL water, dichloromethane extraction 3 times, the anhydrous MgSO of organic phase 4Dried overnight is filtered, and concentrating under reduced pressure obtains crude product, and the normal pressure column chromatography namely gets product.
Main physical and the chemical property of compound (2d) are as follows:
1H?NMR(400MHz,CDCl 3,δ:ppm):6.04(br,1H,NH),5.39-5.34(m,2H,–CH=CH-),3.63(t,J=6Hz,2H,C H 2OH),3.42(q,J=4Hz,2H,NHC H 2),2.97-2.89(m,2H,CH 2),2.22-2.18(m,2H,CH 2),2.13-1.99(m,3H,CH 2,OH),1.71-1.62(m,4H,2CH 2),1.31-1.26(m,20H,10CH 2),0.90-0.87(m,3H,CH 3);
13C NMR (100MHz, CDCl 3, δ: ppm): 174.6 (C=O), 130.0,129.7 (olefinic carbons), 59.2 ( CH 2OH), 36.7 (NH CH 2), 36.2,32.3,31.9,29.8,29.7,29.5,29.3,29.2,29.1,27.2,27.1,25.8,22.6,14.1 ( CH 3);
IR (KBr) ν (cm -1): 3297 (N-H), 2923 (HC=CH), 1637 (C=O), 1549,1463,1271,1053,945,718 (cis-form olefin);
MS?m/z[M+H] +340,314,198;
HRMS (TOF-MS) exact mass calcd for[C 21H 41NO 2+ Na] +Theoretical value 362.3030, measured value 362.3037.
Embodiment 5: preparation linolic acid Propanolamine compound (2e), and the structural formula of compound (2e) is:
Figure BDA00002782046300063
The synthesis step of compound is as follows:
Under the condition of nitrogen protection, add Isosorbide-5-Nitrae-dioxane, 10mmol linolic acid, 12mmol Propanolamine, the 3.0g of 20mL predrainage in 50mL tool plug ground there-necked flask Molecular sieve, then add 0.5g immobilized lipase Novozym435, heated and stirred reaction 24h in 60 ℃ of waters bath with thermostatic control.With the reaction solution elimination solids that obtains, filtrate decompression is concentrated, adds 80mL water, dichloromethane extraction 3 times, the anhydrous MgSO of organic phase 4Dried overnight is filtered, and concentrating under reduced pressure obtains crude product, and the normal pressure column chromatography namely gets product.
Main physical and the chemical property of compound (2e) are as follows:
1H?NMR(400MHz,CDCl 3,δ:ppm):6.12(br,1H,NH),5.40-5.32(m,4H,2–CH=CH-),3.62(t,J=6Hz,2H,C H 2OH),3.42(t,J=6Hz,2H,NHC H 2),2.96-2.77(m,4H,2CH 2),2.21-2.17(m,2H,CH 2),2.05-1.99(m,4H,2CH 2),1.69-1.61(m,2H,CH 2),1.37-1.22(m,15H,7CH 2,OH),0.99-0.86(m,3H,CH 3);
13C NMR (100MHz, CDCl 3, δ: ppm): 174.6 (C=O), 130.2,130.0,128.0,127.9 (olefinic carbons), 59.2 ( CH 2OH), 36.7 (NH CH 2), 36.1,32.3,31.9,31.5,29.8,29.7,29.6,29.5,29.3,29.2,27.2,25.8,22.6,14.0 ( CH 3);
IR (KBr) ν (cm -1): 3305 (N-H), 1924 (HC=CH), 1638 (C=O), 1547,1457,1269,1064,722 (cis-form olefin);
MSm/z[M+H] +338,[M+Na] +360,209,119;
HRMS (TOF-MS) exact mass calcdfor[C 21H 39NO 2+ Na] +Theoretical value 360.2873, measured value 360.2874.
Embodiment 6: preparation timnodonic acid Propanolamine compound (2f), and the structural formula of compound (2f) is:
Figure BDA00002782046300071
The synthesis step of compound is as follows:
Under the condition of nitrogen protection, add Isosorbide-5-Nitrae-dioxane, 10mmol timnodonic acid, 12mmol Propanolamine, the 3.0g of 20mL predrainage in 50mL tool plug ground there-necked flask
Figure BDA00002782046300072
Molecular sieve, then add 0.6g immobilized lipase Novozym435, heated and stirred reaction 36h in 45 ℃ of waters bath with thermostatic control.With the reaction solution elimination solids that obtains, filtrate decompression is concentrated, adds 80mL water, dichloromethane extraction 3 times, the anhydrous MgSO of organic phase 4Dried overnight is filtered, and concentrating under reduced pressure obtains crude product, and the normal pressure column chromatography namely gets product.
Main physical and the chemical property of compound (2f) are as follows:
1H?NMR(400MHz,CDCl 3,δ:ppm):6.02(br,1H,NH),5.43-5.31(m,10H,5CH=CH-),3.63(t,J=6Hz,2H,C H 2OH),3.42(t,J=6Hz,2H,NHC H 2),2.85-2.81(m,8H,4CH 2),2.21-2.15(m,2H,CH 2),2.10-2.05(m,4H,2CH 2),1.75-1.67(m,4H,2CH 2),1.28-1.25(br,1H,OH),1.00-0.89(m,3H,CH 3);
13C NMR (100MHz, CDCl 3, δ: ppm): 174.5 (C=O), 132.1,129.0,128.8,128.6,128.3,128.2,128.0,127.9,127.0 (olefinic carbons), 59.2 ( CH 2OH), 36.2 (NH CH 2), 36.0,32.3,25.7,25.6,25.5,20.6,14.3 ( CH 3);
IR (KBr) ν (cm -1): 3294 (N-H), 3011 (HC=CH), 1642 (C=O), 1549,1445,1264,1066,925,708 (cis-form olefin);
MS?m/z[M+H] +360,[M+Na] +382,312,158;
HRMS (TOF-MS) exact mass calcd for[C 23H 37NO 2+ Na] +Theoretical value 382.2716, measured value 382.2714.
Embodiment 7: preparation docosahexenoic acid Propanolamine compound (2g), and the structural formula of compound (2g) is:
Figure BDA00002782046300081
The synthesis step of compound is as follows:
Under the condition of nitrogen protection, add Isosorbide-5-Nitrae-dioxane, 10mmol docosahexenoic acid, 12mmol Propanolamine, the 3.0g of 20mL predrainage in 50mL tool plug ground there-necked flask
Figure BDA00002782046300082
Molecular sieve, then add 0.6g immobilized lipase Novozym435, heated and stirred reaction 36h in 45 ℃ of waters bath with thermostatic control.With the reaction solution elimination solids that obtains, filtrate decompression is concentrated, adds 80mL water, dichloromethane extraction 3 times, the anhydrous MgSO of organic phase 4Dried overnight is filtered, and concentrating under reduced pressure obtains crude product, and the normal pressure column chromatography namely gets product.
Main physical and the chemical property of compound (2g) are as follows:
1H?NMR(400MHz,CDCl 3,δ:ppm):6.04(br,1H,NH),5.43-5.30(m,12H,6–CH=CH-),3.62(t,J=6Hz,2H,C H 2OH),3.41(q,J=6Hz,2H,NHC H 2),2.89-2.82(m,10H,5CH 2),2.45-2.39(m,2H,CH 2),2.28-2.23(m,2H,CH 2),2.12-2.05(m,2H,CH 2),1.72-1.65(m,2H,CH 2),1.30-1.26(br,1H,OH),1.00-0.90(m,3H,CH 3);
13C NMR (100MHz, CDCl 3, δ: ppm): 173.7 (C=O), 132.0,129.5,128.6,128.3,128.2,128.1,128.0,127.9,127.0 (olefinic carbons), 59.2 ( CH 2OH), 36.4 (NH CH 2), 36.2,36.0,32.3,25.6,25.5,23.5,20.6,14.3 ( CH 3);
IR (KBr) ν (cm -1): 3292 (N-H), 3011 (HC=CH), 1644 (C=O), 1548,1441,1268,1065,926,705 (cis-form olefin);
MS?m/z[M+H] +386,[M+Na] +408,350,227;
HRMS (TOF-MS) exact mass calcd for[C 25H 39NO 2+ Na] +Theoretical value 408.2873, measured value 408.2866.
The therapeutic action of unsaturated polyol fatty acid sulfonamide derivatives to Triton WR-1339 inducing mouse acute hyperlipemia, it uses effect as follows:
80 mouse male and females half and half of 18～22g KM kind are divided into 10 groups at random, 8 every group: blank group; Model group; Medication therapy groups.
Blank group: the water miscible liquid 1.0mL that per os gavage 1% Xylo-Mucine forms.
Model group: per os gavage Triton WR-13390.5mL (dosage is 400mg/kg), the water miscible liquid 0.5mL of per os gavage 1% Xylo-Mucine formation at once afterwards.
Medication therapy groups: per os gavage Triton WR-13390.5mL (dosage is 400mg/kg), per os gavage 0.5mL unsaturated polyol fatty acid sulfonamide derivatives (2a, 2b, 2c, 2d, 2e, 2f, 2g, dosage are 100mg/kg) at once afterwards.
After Triton WR-1339 injection 18h, eyeball is got blood, and separation of serum is pressed the triglyceride content (table 1, Fig. 7) that kit method is measured mice serum.Can find out from the experimental result of table 1, the unsaturated polyol fatty acid sulfonamide derivatives can reduce the content of model mice triglyceride in serum to some extent.
The impact of table 1 unsaturated polyol fatty acid sulfonamide derivatives on mice serum triglyceride content
Figure BDA00002782046300091
Below provide docosahexenoic acid thanomin (2c) compound and taken in the impact of forage volume and body weight gain the day of Diet hyperlipemia in mice.
Animal is in testing preadaptation 1 week of raising: 23 ± 1 ℃ of temperature, and humidity: 40%～60%, natural lighting is freely drunk water, the ad lib feed.KM kind mouse is divided into 3 groups at random, 10 every group, is designated as respectively Normal group, model group with hyperlipemia, docosahexenoic acid thanomin administration group.Except Normal group gave normal diet, all the other groups all gave high lipid food.The high lipid food formula is: 10% lard, 20% sucrose, 2% cholesterol, 0.3% cholate, 67.7% conventional feed.The dosage of docosahexenoic acid thanomin administration group per os every morning gavage 100mg/kg.Bluntness (%)=(test group ABW-control group mean body weight)/control group mean body weight * 100%, body weight gain rate=(end-body weight-first body weight)/first body weight.
Record the feed intake of every group of mouse every day, feed continuously after 30 days, data to record are added up, data presentation: every mouse of Normal group is 7.7g to the per day intake of normal diet, every mouse of model group with hyperlipemia is 10.2g to the per day intake of normal diet, every mouse of docosahexenoic acid thanomin administration group is 6.5g to the per day intake of normal diet, description of test, docosahexenoic acid thanomin can obviously suppress the appetite of mouse really.
Simultaneously, every body weight that took a mouse in 3 days, record data, to the weight data curve plotting of mouse as shown in Figure 8, as can be seen from Figure 8, hyperlipidemia model group Mouse Weight is higher than normal group, but otherness is remarkable (P＞0.05) not, hyperlipidemia model group mouse reaches 9.7% with respect to the normal group bluntness, and administration group mouse is-8.03% with respect to the bluntness of normal group, has namely lost weight 8.03%.The body weight gain rate (150.5%) of administration group is all lower than model group (187.6%) and normal group (175.6%) mouse.Illustrate that this given the test agent 2c has obvious restraining effect to the increase of obesity mice body weight.

Claims (10)

1. unsaturated polyol fatty acid sulfonamide derivatives is characterized in that its general structure is as follows:
Figure FDA00002782046200011
Wherein, n=0,3,6; M=1,2,5,6; L=2,3,7; K=2,3.
2. a kind of unsaturated polyol fatty acid sulfonamide derivatives as claimed in claim 1, is characterized in that it comprises linolic acid thanomin (2a), timnodonic acid thanomin (2b), docosahexenoic acid thanomin (2c), oleic acid Propanolamine (2d), linolic acid Propanolamine (2e), timnodonic acid Propanolamine (2f), docosahexenoic acid Propanolamine (2g).
3. a kind of preparation method of unsaturated polyol fatty acid sulfonamide derivatives as claimed in claim 1 is characterized in that comprising the following steps:
1) under the condition of nitrogen protection, add in tool plug ground there-necked flask predrainage organic solvent, unsaturated fatty acids, amine,
Figure FDA00002782046200012
Molecular sieve, then add immobilized lipase Novozym435, heat the building-up reactions of dewatering in water-bath, get reaction solution;
2) the reaction solution elimination solids that step 1) is obtained, filtrate decompression is concentrated, adds entry and methylene dichloride, after extraction, the anhydrous MgSO of organic phase 4Drying is filtered, and concentrating under reduced pressure obtains crude product, and the normal pressure column chromatography namely gets product.
4. a kind of preparation method of unsaturated polyol fatty acid sulfonamide derivatives as claimed in claim 3, is characterized in that in step 1), the organic solvent of described predrainage, unsaturated fatty acids, amine,
Figure FDA00002782046200013
The proportioning of molecular sieve is: the organic solvent 20mL of predrainage: unsaturated fatty acids 10mmol: amine (10～15) mmol:
Figure FDA00002782046200014
Molecular sieve (2～5) g.
5. a kind of preparation method of unsaturated polyol fatty acid sulfonamide derivatives as claimed in claim 3, is characterized in that in step 1), and the add-on of described immobilized lipase Novozym435 is 0.5～1g.
6. a kind of preparation method of unsaturated polyol fatty acid sulfonamide derivatives as claimed in claim 3, is characterized in that in step 1), and described organic solvent is selected from a kind of in methylene dichloride, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, glycol dimethyl ether.
7. a kind of preparation method of unsaturated polyol fatty acid sulfonamide derivatives as claimed in claim 3, is characterized in that in step 1), and described unsaturated fatty acids is selected from a kind of in oleic acid, linolic acid, timnodonic acid, docosahexenoic acid; Described amine is selected from a kind of in thanomin, Propanolamine; Described unsaturated fatty acids and amine are 1 in molar ratio: (1～1.5).
8. a kind of preparation method of unsaturated polyol fatty acid sulfonamide derivatives as claimed in claim 3, is characterized in that in step 1), and the temperature of described water bath with thermostatic control is 40～60 ℃; The described reaction times can be 10～36h.
9. a kind of preparation method of unsaturated polyol fatty acid sulfonamide derivatives as claimed in claim 3, is characterized in that in step 2) in, the reaction solution elimination solids that described step 1) obtains is to adopt sand core funnel elimination solids; Described extraction can extract 2～3 times; Described column chromatography, its column packing can be selected from silica gel, AgNO 3, CuCl 2In at least a, as adopting silica gel and AgNO 3, or CuCl 2And silica gel, in mass ratio, AgNO 3: silica gel=1: (2～10), CuCl 2: silica gel=1: 300～400 order silica gel can be adopted in (2～5), described silica gel.
10. the unsaturated polyol fatty acid sulfonamide derivatives is used in the preparation weight reduction product as claimed in claim 1.
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CN105230617A (en) * 2015-09-25 2016-01-13 浙江大学 Applications of linoleoylethanolamine in improvement of gray mold resistance and bacterial leaf spot resistance of plants
CN105230617B (en) * 2015-09-25 2017-05-10 浙江大学 Applications of linoleoylethanolamine in improvement of gray mold resistance and bacterial leaf spot resistance of plants
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CN106350549A (en) * 2016-07-31 2017-01-25 江南大学 Method for preparing fatty acid monoethanolamide by aid of enzymatic processes
CN106350549B (en) * 2016-07-31 2019-11-29 江南大学 A kind of method that enzyme process prepares fatty monoethanol amide
CN109796367A (en) * 2019-03-29 2019-05-24 广东工业大学 A kind of preparation method and applications of N- fatty acyl ethanolamine product
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