CN105503652A - Cyano-containing resveratrol analogue and preparation method and purpose thereof - Google Patents

Cyano-containing resveratrol analogue and preparation method and purpose thereof Download PDF

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CN105503652A
CN105503652A CN201511016946.8A CN201511016946A CN105503652A CN 105503652 A CN105503652 A CN 105503652A CN 201511016946 A CN201511016946 A CN 201511016946A CN 105503652 A CN105503652 A CN 105503652A
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cyano
containing resveratrol
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田玉顺
马军
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Yanbian University
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Abstract

The invention provides a cyano-containing resveratrol analogue and a preparation method and application thereof, and relates to the field of medical compounds. A structure of the cyano-containing resveratrol analogue is shown in the formula of the description; 3,5-dihydroxy-benzoic acid is mainly used as a raw material, and the cyano-containing resveratrol analogue is prepared by the following steps of methylation, reduction, brominating, Abozove rearrangement, Wittig-Hornor reaction and Knoevenegal reaction; in the preparation process of the cyano-containing resveratrol analogue, the chemical substances with lower toxicity, such as trimethylsilyl cyanide and tetrabutylammonium fluoride, are used for replacing chemicals with higher toxicity, such as sodium cyanide or potassium cyanide, to introduce cyano, so that the damage to the health of an operator is greatly decreased, and the serious harm to environments is avoided. The preparation method has the advantages that the yield is higher, the environment-friendly effect is good, and multiple types of cyano-containing resveratrol analogue with anti-cancer activity on cells can be obtained.

Description

Cyano-containing resveratrol analogs and its production and use
Technical field
The present invention relates to medicinal compound field, particularly cyano-containing resveratrol analogs and its production and use.
Background technology
Trans-resveratrol is the biological very strong natural polyphenol class material that one is mainly derived from the plants such as grape (red wine), giant knotweed, peanut, mulberry fruit, is also called resvertrol.Being the chemopreventive agent of tumour, is also reduce platelet aggregation, the chemopreventive agent of prevention and therapy atherosclerosis, cardiovascular and cerebrovascular diseases.The chemical name of trans-resveratrol is (E)-3,5,4-trihydrolystilbene, and chemical structure is as shown in structural formula 1:
Trans-resveratrol
Structural formula 1
1993, the research such as Jayafilake showed that trans-resveratrol has antitumour activity, and its reason is that they can the activity of arrestin matter-Tyrosylprotein kinase.Trans-resveratrol has antitumour activity and shows: one, suppress initiation: reduce free radical and formed, induce II phase medicine to increase for enzyme, the effect of antagonism Dioxins; Two, suppress enhancement effect: suppress cyclooxygenase (COX), suppress catalase; Three, the effect of holding back the development: anticancer is bred, inducing cancer cell breaks up, cancer cell specific induction of apoptosis.Many medical researches find that trans-resveratrol all has obvious restraining effect to Several Kinds of Malignancy cells such as mammary cancer, cancer of the stomach, colorectal carcinoma, prostate cancer, leukemia, ovarian cancer, skin carcinomas, also can there is prophylactic effect to osteoporosis, acne and senile dementia, there is antiviral and immunoregulation effect.Trans-resveratrol also works to the anti-ageing enzyme of a kind of monomer of inside of human body, has the latent effect extending predicted life.
Be a kind of confirmed natural antitumor prodrug got a good chance of based on trans-resveratrol just, people expect to search out cancer therapy drug more safely and effectively by carrying out chemically modified to trans-resveratrol parent molecule.Find in the process that two phenyl ring of trans-resveratrol parent are modified, its antitumour activity is also not obvious, and introduce in carboxyl, heterocycle or cyano group process in its ethylene unit, find that the molecule antitumour activity after introducing cyano group is obviously better than other groups, and effectively avoid the isomerization of vinyl.Chinese invention patent application publication number CN1687021 discloses a kind of 1-cyano group-1-(3,5-dimethoxy phenyl)-2-(4-R base phenyl) ethene and preparation method thereof, and structural formula and the synthetic route thereof of product are as follows:
1-cyano group-1-(3,5-dimethoxy phenyl)-2-(4-R base phenyl) ethene
Structural formula 2
Synthetic route 1
This preparation method is to when trans-resveratrol ethylene unit introduces cyano group, the highly toxic substances such as sodium cyanide (NaCN) or potassium cyanide (KCN) are used to carry out cyanation, although its reaction effect is better, but reaction needed is carried out 2 hours or more, the time exposed by prussiate is longer, cause operation inconvenience in experimentation, very large to the Health hazard of operator; And after having tested, " three wastes " process is very difficult, deals with improperly and seriously can cause environmental pollution; The management of the reagent such as sodium cyanide or potassium cyanide is very strict in addition, and purchase approach is narrow, applies limited, is not suitable for suitability for industrialized production.
Summary of the invention
For the deficiencies in the prior art, the invention provides cyano-containing resveratrol analogs and its production and use, substitute the severe poisonous chemicals such as sodium cyanide or potassium cyanide by using trimethylsilyl cyanide and the lower chemical substance of this type of toxicity of tetrabutyl ammonium fluoride and introduce cyano group, significantly reduce the injury to operator's health, it also avoid and serious harm is caused to environment, more cyano-containing resveratrol analogs cell being had to antitumour activity of kind can be obtained simultaneously.
For realizing above object, the present invention is achieved by the following technical programs:
Cyano-containing resveratrol analogs, its general structure is as shown in structural formula 3:
Structural formula 3
In structural formula 3, the R on phenyl ring is p-F, p-Cl, p-Br, o-Cl, o-Br, p-N (CH 3) 2, p-OBn, p-CH 3, p-CH 2cH 3, p-OCH 2cH 3, p-OCH 2cH 2cH 3, p-OCH (CH 3) 2, p-O (CH 2) 3cH 3, p-OCH 2cH (CH 3) 2, p-O (CH 2) 4cH 3, p-O (CH 2) 2cH (CH 3) 2, p-O (CH 2) 5cH 3, o-OCH 2cH 3, o-OCH 2cH 2cH 3, o-OCH (CH 3) 2, o-O (CH 2) 3cH 3, o-CH 2cH (CH 3) 2, o-O (CH 2) 4cH 3, o-O (CH 2) 5cH 3, m-OCH 2cH 3(wherein p is phenyl ring para-orientation, m be between phenyl ring position replace, o be phenyl ring ortho position replace, Bn is benzyl) in any one.
Further, described cyano-containing resveratrol analogs, its another kind of structural formula is as shown in structural formula 4:
Structural formula 4
Further, described cyano-containing resveratrol analogs, its another kind of general structure is as shown in structural formula 5:
Structural formula 5
In structural formula 5, X is any one in S, O.
The method preparing cyano-containing resveratrol analogs of the present invention is: its synthetic route is as follows:
Synthetic route 2
Synthesis step is as follows:
1. get 3,5-resorcylic acid, salt of wormwood and acetone in 500mL reaction unit, slowly at the uniform velocity drip methyl-sulfate with constant pressure funnel; Heating is started, backflow after dripping off; Adopt thin-layer chromatography tracing detection, react complete and be cooled to room temperature; Filter, washing with acetone filter residue merging filtrate, anhydrous sodium sulfate drying, removes solvent under reduced pressure, dry, obtains compound 2;
2. under argon shield and condition of ice bath, add lithium aluminum hydride and anhydrous tetrahydro furan successively in 100mL there-necked flask, stir, drip the tetrahydrofuran solution of compound 2 with syringe, remove ice bath, continue at room temperature reaction, thin-layer chromatography tracing detection, waits and reacts complete slowly being poured into by reaction solution in 200mL frozen water, stirs, there is flocks, by diluted hydrochloric acid dissolution precipitation, extraction into ethyl acetate, with anhydrous sodium sulfate drying, remove ethyl acetate under reduced pressure, dry compound 3;
3., under ice bath and argon shield, anhydrous CH is dissolved in 2cl 23,5-3,5-dimethoxybenzoic alcohols in reaction unit, slowly drip the PBr being dissolved in dichloromethane solution while stirring with syringe 3transfer room temperature to after ice bath reaction, continue reaction, thin-layer chromatography tracing detection, complete by reaction solution impouring 50mL frozen water Deng reaction, stir, lower floor is milky white liquid, adds sodium bicarbonate and adjusts pH to 7, be extracted with ethyl acetate after dividing water-yielding stratum, anhydrous sodium sulfate drying, removes solvent under reduced pressure, dry compound 4;
4. successively by dimethoxy bromobenzyl, trimethylsilyl cyanide, tetrabutyl ammonium fluoride and acetonitrile in reaction unit, stir, be warming up to backflow 6h, thin-layer chromatography tracing detection, is cooled to room temperature, in reaction solution impouring 100mL frozen water, stir, separate out white solid, filter, solid 50% methanol wash, dry compound 5;
5. any one in 3,5-dimethoxybenzeneacetonitriles and aromatic aldehyde, substituted aroma aldehyde, pyridine aldehydes, Furan Aldehydes, thiophene aldehyde reacts and generates cyano-containing resveratrol analogs in methyl alcohol and sodium methylate.
The purposes of cyano-containing resveratrol analogs, cyano-containing resveratrol analogs has antitumour activity in the preliminary screening of HCT116, HeLa, BEL-7402 and L02 tetra-kinds of cells.In cyano-containing resveratrol analogs, A ring is 3, the trans-resveratrol structure of 5-dimethoxy phenyl ring, 4, B ring has oxyethyl group, propoxy-, isopropoxy, dimethylamino, methyl, ethyl, 2 have bromine, chlorine, have very strong antitumour activity when B ring is thiphene ring, furan nucleus and pyridine ring to HCT116 human colon cancer cell.What have oxyethyl group, propoxy-to replace when 4, B ring is the strong to BEL-7402 human hepatoma cell proliferation inhibit activities of furan nucleus with B ring, but weak to the proliferation inhibition activity of human normal liver cell L 02, they are all to BEL-7402 human liver cancer cell and the selective restraining effect of human normal liver cell L 02.
Further, described cyano-containing resveratrol analogs, is applied to cancer therapy drug.
Cyano group is introduced by using the lower chemical substance of the toxicity such as trimethylsilyl cyanide and tetrabutyl ammonium fluoride to substitute the severe poisonous chemicals such as sodium cyanide or potassium cyanide in the preparation process of cyano-containing resveratrol analogs of the present invention, alleviate the injury to operator's health greatly, also avoid causing serious harm to environment, more cyano-containing resveratrol analogs cell being had to antitumour activity of kind can be obtained simultaneously.This preparation method's productive rate is higher, environmentally friendly, applied range.
Embodiment
For making the object of the embodiment of the present invention, technical scheme and advantage clearly, below in conjunction with embodiments of the invention, the technical scheme in the embodiment of the present invention is clearly and completely described.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
Below in conjunction with embodiment, the present invention is further illustrated.
The preparation of embodiment 1:Z-2-(3,5-dimethoxy phenyl)-3-(4-fluorophenyl) vinyl cyanide
The synthesis of intermediate product 3,5-dimethoxy p-methyl 2
14.231g (0.092mol) 3,5-resorcylic acid 1, salt of wormwood 26.021g (0.189mol) and 100mL acetone, in 500mL two mouthfuls of flasks, slowly at the uniform velocity drip 17mL methyl-sulfate with constant pressure funnel; Heating is started, backflow 4h after about 30min drips off; Adopt thin-layer chromatography tracing detection, react complete and be cooled to room temperature; Filter, washing with acetone filter residue merging filtrate, anhydrous sodium sulfate drying, removes solvent under reduced pressure, dry, obtains compound 2; Receive 90.7%, fusing point is 41 ~ 43 DEG C. 1HNMR(300MHz,CDCl 3):δ7.18(d,J＝2.3Hz,2H),6.64(t,J＝2.3Hz,1H),3.90(s,3H),3.82(s,6H)。
The synthesis of intermediate product 3,5-3,5-dimethoxybenzoic alcohol 3
Under argon shield and condition of ice bath, add lithium aluminum hydride 1.251g (0.033mol) and 20mL anhydrous tetrahydro furan successively in 100mL there-necked flask, stir, the tetrahydrofuran solution 20mL of 5.886g (0.03mol) compound 2 is dripped with syringe, remove ice bath, continue at room temperature reaction 4h, thin-layer chromatography tracing detection, complete reaction solution is slowly poured in 200mL frozen water Deng reaction, stir, there is flocks, precipitate with diluted hydrochloric acid dissolution, extraction into ethyl acetate, with anhydrous sodium sulfate drying, remove ethyl acetate under reduced pressure, dry compound 3, yield is 81.1%, fusing point is 46 ~ 50 DEG C. 1HNMR(300MHz,CDCl 3):δ6.53(s,2H),6.38(s,1H),4.63(s,2H),3.79(s,6H),1.87(s,1H)。
The synthesis of intermediate product 3,5-dimethoxy bromobenzyl 4
Under ice bath and argon shield, be dissolved in the anhydrous CH of 20mL 2cl 24.088g (0.024mol) 3, 5-3,5-dimethoxybenzoic alcohol 3 is in 100mL tri-mouthfuls of round-bottomed flasks, the 2.54mLPBr3 being dissolved in 10mL dichloromethane solution is slowly dripped while stirring with syringe, room temperature is transferred to after ice bath reaction 2h, continue reaction 2-3h, thin-layer chromatography tracing detection, complete by reaction solution impouring 50mL frozen water Deng reaction, stir, lower floor is milky white liquid, add sodium bicarbonate and adjust pH to 7, be extracted with ethyl acetate after dividing water-yielding stratum, anhydrous sodium sulfate drying, remove solvent under reduced pressure, dry compound 4, yield is 85.4%, fusing point is 69 ~ 70 DEG C. 1HNMR(300MHz,CDCl 3):δ6.54(s,2H),6.40(s,1H),4.42(s,2H),3.79(d,J＝5.5Hz,6H)。
The synthesis of intermediate product 3,5-dimethoxybenzeneacetonitrile 5
Successively by 2.310g (0.01mol) 3,5-dimethoxy bromobenzyl 4, trimethylsilyl cyanide 1.485g (0.015mol), tetrabutyl ammonium fluoride 4.725g (0.015mol) and 30ml acetonitrile are in 100mL there-necked flask, stir, be warming up to backflow 6h, thin-layer chromatography tracing detection, be cooled to room temperature, in reaction solution impouring 100mL frozen water, stir, separate out white solid, filter, solid 50% methanol wash, dry compound 5, yield is 66.7%, and fusing point is 52-53 DEG C. 1HNMR(300MHz,CDCl 3):δ6.46(d,J＝2.2Hz,2H),6.40(t,J＝2.2Hz,1H),3.79(s,6H),3.68(s,2H)。
The preparation of Z-2-(3,5-dimethoxy phenyl)-3-(4-fluorophenyl) vinyl cyanide 6a, reaction equation is as follows:
Add 0.01mol3 in 50mL there-necked flask, 5-dimethoxybenzeneacetonitrile 5,0.01mol4-fluorobenzaldehyde and 20mL methyl alcohol, stir and be warming up to 60 DEG C, add sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, is cooled to room temperature after question response, filter, washing, dry, obtain colourless acicular crystal by recrystallizing methanol, yield is 40.4%, and fusing point is 113-115 DEG C. 1HNMR(300MHz,CDCl 3):δ7.75(d,J＝8.5Hz,2H),7.60(d,J＝8.6Hz,2H),7.45(s,1H),6.79(d,J＝2.2Hz,2H),6.50(t,J＝2.2Hz,1H),3.85(s,6H)。
The preparation of embodiment 2:Z-2-(3,5-dimethoxy phenyl)-3-(4-chloro-phenyl-) vinyl cyanide 6b, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-chlorobenzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain white solid by recrystallizing methanol, yield is 73.9%, and fusing point is 114-116 DEG C. 1HNMR(300MHz,CDCl 3):δ7.82(d,J＝8.6Hz,2H),7.46(d,J＝4.6Hz,2H),7.42(s,1H),6.79(d,J＝2.1Hz,2H),6.49(dd,J＝6.0,3.9Hz,1H),3.85(s,6H)。
The preparation of embodiment 3:Z-2-(3,5-dimethoxy phenyl)-3-(4-bromophenyl) vinyl cyanide 6c, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-bromobenzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow solid by recrystallizing methanol, yield is 66.3%, and fusing point is 150-152 DEG C. 1HNMR(300MHz,CDCl 3)δ7.91(d,J＝5.4Hz,2H),7.48(s,1H),7.16(t,J＝8.6Hz,2H),6.79(d,J＝2.2Hz,2H),6.50(t,J＝2.2Hz,1H),3.85(s,6H)。13CNMR(75MHz,CDCl3):δ161.27,141.08,136.14,132.45,132.23,130.71,124.95,117.72,112.33,104.32,101.43,55.57。IR(KBr)cm -1:2835(-OCH3),2220(-CN),858(-C＝C-H)。MS-EI:m/z:342(M+1) +。
The preparation of embodiment 4:Z-2-(3,5-dimethoxy phenyl)-3-(2-chloro-phenyl-) vinyl cyanide 6d, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-chlorobenzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain colourless acicular crystal by recrystallizing methanol, yield is 74.1%, and fusing point is 84-86 DEG C. 1HNMR(300MHz,CDCl 3):δ8.09(s,1H),7.87(s,1H),7.43(d,J＝24.9Hz,3H),6.84(s,2H),6.52(s,1H),3.84(s,6H)。
The preparation of embodiment 5:Z-2-(3,5-dimethoxy phenyl)-3-(2-bromophenyl) vinyl cyanide 6e, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-bromobenzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain colourless acicular crystal by recrystallizing methanol, yield is 73.8%, and fusing point is 180-182 DEG C. 1HNMR(300MHz,CDCl 3):δ8.58(s,1H),8.41–8.27(m,2H),7.74–7.65(m,1H),7.58(s,1H),6.82(s,2H),6.54(s,1H),3.86(s,6H)。
The preparation of embodiment 6:Z-2-(3,5-dimethoxy phenyl)-3-(4-diformazan aminophenyl) vinyl cyanide 6f, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-dimethylaminobenzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain yellow needle-like crystals by recrystallizing methanol, yield is 53.2%, and fusing point is 76-78 DEG C. 1HNMR(300MHz,CDCl 3):δ7.85(d,J＝9.0Hz,2H),7.40(s,1H),6.77(d,J＝2.2Hz,2H),6.72(d,J＝9.0Hz,2H),6.43(d,J＝2.1Hz,1H),3.84(s,6H),3.06(s,6H)。13CNMR(75MHz,CDCl3):δ161.12,151.73,142.92,137.70,131.42,121.41,119.44,111.60,104.35,103.74,100.17,55.51,40.05。IR(KBr)cm -1:2837(-OCH3),2204(-CN),841(-C＝C-H)。MS-EI:m/z:308(M+1) +。
The preparation of embodiment 7:Z-2-(3,5-dimethoxy phenyl)-3-(4-benzyl oxy phenyl) vinyl cyanide 6g, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-benzoxybenzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain white needle-like crystals by recrystallizing methanol, yield is 47.9%, and fusing point is 90-92 DEG C. 1HNMR(300MHz,CDCl 3):δ7.88(d,J＝8.8Hz,2H),7.39(ddd,J＝8.4,7.2,3.4Hz,5H),7.05(d,J＝8.8Hz,2H),6.79(d,J＝2.2Hz,2H),6.47(t,J＝2.1Hz,1H),5.13(s,2H),3.85(s,6H)。
The preparation of embodiment 8:Z-2-(3,5-dimethoxy phenyl)-3-(4-tolyl) vinyl cyanide 6h, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-tolyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain white needle-like crystals by recrystallizing methanol, yield is 74.9%, and fusing point is 78-80 DEG C. 1HNMR(300MHz,CDCl 3):δ7.79(d,J＝8.2Hz,2H),7.49(s,1H),7.29(s,2H),6.80(d,J＝2.2Hz,2H),6.48(t,J＝2.2Hz,1H),3.85(s,6H),2.41(s,3H)；MS-EI:m/z:279(M+1) +。
The preparation of embodiment 9:Z-2-(3,5-dimethoxy phenyl)-3-(4-ethylbenzene) vinyl cyanide 6i, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-ethylbenzene formaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain white needle-like crystals by recrystallizing methanol, yield is 86.1%, and fusing point is 66-68 DEG C. 1HNMR(300MHz,CDCl 3):δ7.82(d,J＝7.9Hz,2H),7.50(s,1H),7.30(d,J＝7.9Hz,2H),6.81(s,2H),6.49(d,J＝2.0Hz,1H),3.86(d,J＝5.6Hz,6H),2.71(d,J＝7.5Hz,2H),1.27(dd,J＝10.5,4.6Hz,3H)。MS-EI:m/z:309(M+1) +。
The preparation of embodiment 10:Z-2-(3,5-dimethoxy phenyl)-3-(4-phenelyl) vinyl cyanide 6j, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-ethoxy-benzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain white needle-like crystals by recrystallizing methanol, yield is 65.3%, and fusing point is 98-100 DEG C. 1HNMR(300MHz,CDCl 3)：δ8.02-7.80(m,2H)，7.44(s,1H)，7.06–6.90(m,2H)，6.78(d,J＝2.0Hz,2H)，6.46(d,J＝2.0Hz,1H)，4.09(dd,J＝13.9,6.9Hz,2H)，3.81(d,J＝14.3Hz,6H)，1.44(t,J＝7.0Hz,3H)。 13CNMR(75MHz,CDCl 3)：δ161.19,142.34,136.97,131.31,126.13,118.57,114.88,108.27,104.07,100.79,69.70,55.53,22.49,10.49。IR(KBr)cm -1:2835(-OCH 3),2210(-CN),841(-C＝C-H)。MS-EI：m/z:309(M+1) +。
The preparation of embodiment 11:Z-2-(3,5-dimethoxy phenyl)-3-(the positive propoxy phenyl of 4-) vinyl cyanide 6k, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-positive propoxy phenyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain white needle-like crystals by recrystallizing methanol, yield is 62.4%, and fusing point is 82 ~ 83 DEG C. 1HNMR(300MHz,CDCl 3):δ7.87(d,J＝8.7Hz,2H)，7.44(s,1H)，6.96(d,J＝8.8Hz,2H)，6.78(d,J＝2.1Hz,2H)，6.47(d,J＝2.0Hz,1H)，4.10-3.92(m,2H)，3.84(s,6H)，1.84(dq,J＝14.2,7.0Hz,2H)，1.06(t,J＝7.4Hz,3H)。13CNMR(75MHz,CDCl3):δ161.19,160.92,142.33,136.96,131.32,126.17,118.56,114.85,108.31,104.07,100.78,63.71,55.53,14.72。IR(KBr)cm -1:2839(-OCH3),2208(-CN),847(-C＝C-H)。MS-EI:m/z:323(M+1) +。
The preparation of embodiment 12:Z-2-(3,5-dimethoxy phenyl)-3-(4-o-phenyl-isopropyl) vinyl cyanide 6l, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-isopropoxide benzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain white needle-like crystals by recrystallizing methanol, yield is 56.3%, and fusing point is 66-68 DEG C. 1HNMR(300MHz,CDCl 3):δ7.87(d,J＝8.7Hz,2H)，7.44(s,1H)，6.96(d,J＝8.8Hz,2H)，6.78(d,J＝2.1Hz,2H)，6.47(d,J＝2.0Hz,1H)，4.10-3.92(m,2H)，3.84(s,6H)，1.84(dq,J＝14.2,7.0Hz,2H)，1.06(t,J＝7.4Hz,3H)。
The preparation of embodiment 13:Z-2-(3,5-dimethoxy phenyl)-3-(the positive butoxyphenyl of 4-) vinyl cyanide 6m, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-n-butoxy phenyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow solid by recrystallizing methanol, yield is 60.9%, and fusing point is 68 ~ 69 DEG C. 1HNMR(300MHz,CDCl 3):δ7.87(d,J＝7.2Hz,2H)，7.45(s,1H)，6.96(d,J＝7.1Hz,2H)，6.78(d,J＝1.7Hz,2H)，6.47(d,J＝1.9Hz,1H)，4.03(dd,J＝6.4,5.1Hz,2H)，3.84(d,J＝1.5Hz,6H)，1.80(dt,J＝13.3,6.5Hz,2H)，1.51(dd,J＝14.1,6.8Hz,2H)，1.04-0.95(m,3H)。
The preparation of embodiment 14:Z-2-(3,5-dimethoxy phenyl)-3-(the different butoxyphenyl of 4-) vinyl cyanide 6n, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-isobutoxy phenyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain white needle-like crystals by recrystallizing methanol, yield is 62.5%, and fusing point is 58-60 DEG C. 1HNMR(300MHz,CDCl 3):δ7.86(d,J＝8.8Hz,2H),7.45(s,1H),6.96(d,J＝8.8Hz,2H),6.78(d,J＝2.1Hz,2H),6.47(d,J＝2.1Hz,1H),3.84(s,6H),3.78(d,J＝6.5Hz,2H),2.11(t,J＝10.0Hz,1H),1.04(d,J＝6.7Hz,6H)。
The preparation of embodiment 15:Z-2-(3,5-dimethoxy phenyl)-3-(the positive penta oxygen phenyl of 4-) vinyl cyanide 6o, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-n-pentyloxy phenyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow needles by recrystallizing methanol, yield is 66.7%, and fusing point is 52-54 DEG C. 1HNMR(300MHz,CDCl 3):δ7.84(dd,J＝11.8,8.9Hz,2H),7.44(s,1H),6.96(d,J＝8.9Hz,2H),6.76(dd,J＝15.6,5.6Hz,2H),6.47(t,J＝2.2Hz,1H),4.10–3.95(m,2H),3.84(s,6H),1.93–1.74(m,2H),1.53–1.32(m,4H),0.94(t,J＝7.1Hz,3H)。
The preparation of embodiment 16:Z-2-(3,5-dimethoxy phenyl)-3-(4-isoamyl oxygen phenyl) vinyl cyanide 6p, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol4-isopentyloxy phenyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow needles by recrystallizing methanol, yield is 55.2%, and fusing point is 62-64 DEG C. 1HNMR(300MHz,CDCl 3)：δ7.87(d,J＝8.8Hz,2H),7.45(s,1H),6.96(d,J＝8.9Hz,2H),6.78(d,J＝2.2Hz,2H),6.47(d,J＝2.2Hz,1H),4.05(t,J＝6.6Hz,2H),3.84(s,6H),1.84(dd,J＝13.6,6.6Hz,1H),1.71(d,J＝6.6Hz,2H),0.98(d,J＝6.6Hz,6H)。
The preparation of embodiment 17:Z-2-(3,5-dimethoxy phenyl)-3-(the just own oxygen phenyl of 4-) vinyl cyanide 6q, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), the positive hexyloxybenzaldehyde of 0.01mol4-and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain yellow needle-like crystals by recrystallizing methanol, yield is 59.3%, and fusing point is 64 ~ 65 DEG C. 1HNMR(300MHz,CDCl 3):δ7.86(d,J＝8.8Hz,2H)，7.44(s,1H)，6.96(d,J＝8.8Hz,2H)，6.77(t,J＝5.8Hz,2H)，6.49-6.44(m,1H)，4.01(t,J＝6.5Hz,2H)，3.82(d,J＝13.1Hz,6H)，1.79(dd,J＝14.7,6.8Hz,2H)，1.47(s,2H)，1.38-1.31(m,4H)，0.91(t,J＝6.4Hz,3H)。
The preparation of embodiment 18:Z-2-(3,5-dimethoxy phenyl)-3-(2-phenelyl) vinyl cyanide 6r, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-ethoxy-benzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow needles by recrystallizing methanol, yield is 31.7%, and fusing point is 52-54 DEG C. 1HNMR(300MHz,CDCl 3):δ8.13(d,J＝7.8Hz,1H),7.97(s,1H),7.46–7.34(m,1H),7.04(t,J＝7.6Hz,1H),6.93(t,J＝7.0Hz,1H),6.83(d,J＝2.2Hz,2H),6.50(dd,J＝6.8,4.7Hz,1H),4.11(q,J＝7.0Hz,2H),3.82(d,J＝15.9Hz,6H),1.44(dd,J＝9.8,4.1Hz,3H)。
The preparation of embodiment 19:Z-2-(3,5-dimethoxy phenyl)-3-(the positive propoxy phenyl of 2-) vinyl cyanide 6s, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-positive propoxy phenyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow needles by recrystallizing methanol, yield is 46.4%, and fusing point is 52-54 DEG C. 1HNMR(300MHz,CDCl 3):δ8.16(d,J＝7.6Hz,1H),8.00(s,1H),7.39(t,J＝8.7Hz,1H),7.05(t,J＝6.2Hz,1H),6.93(d,J＝8.3Hz,1H),6.83(d,J＝2.2Hz,2H),6.49(d,J＝2.2Hz,1H),4.00(t,J＝6.5Hz,2H),3.85(s,6H),1.85(dd,J＝13.0,5.8Hz,2H),1.06(t,J＝7.4Hz,3H)。
The preparation of embodiment 20:Z-2-(3,5-dimethoxy phenyl)-3-(2-o-phenyl-isopropyl) vinyl cyanide 6t, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-isopropoxide benzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow needles by recrystallizing methanol, yield is 50.4%, and fusing point is 46-48 DEG C. 1HNMR(300MHz,CDCl 3):δ7.86(d,J＝8.8Hz,2H)，7.44(s,1H)，6.96(d,J＝8.8Hz,2H)，6.77(t,J＝5.8Hz,2H)，6.49-6.44(m,1H)，4.01(t,J＝6.5Hz,2H)，3.82(d,J＝13.1Hz,6H)，1.79(dd,J＝14.7,6.8Hz,2H)，1.47(s,2H)，1.38-1.31(m,4H)，0.91(t,J＝6.4Hz,3H)。
The preparation of embodiment 21:Z-2-(3,5-dimethoxy phenyl)-3-(the positive butoxyphenyl of 2-) vinyl cyanide 6u, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-n-butoxy phenyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow needles by recrystallizing methanol, yield is 24.3%, and fusing point is 44-46 DEG C. 1HNMR(300MHz,CDCl 3):δ8.18(d,J＝7.6Hz,1H),8.03(s,1H),7.39(t,J＝7.8Hz,1H),7.05(t,J＝7.5Hz,1H),6.92(d,J＝8.1Hz,1H),6.83(s,2H),6.49(s,1H),3.85(s,6H),3.80(s,2H),2.26–2.05(m,1H),1.06(d,J＝6.6Hz,6H)。
The preparation of embodiment 22:Z-2-(3,5-dimethoxy phenyl)-3-(the different butoxyphenyl of 2-) vinyl cyanide 6v, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-isobutoxy phenyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow needles by recrystallizing methanol, yield is 62.3%, and fusing point is 35-36 DEG C. 1HNMR(300MHz,CDCl 3):δ8.18(d,J＝7.6Hz,1H),8.03(s,1H),7.39(t,J＝7.8Hz,1H),7.05(t,J＝7.5Hz,1H),6.92(d,J＝8.1Hz,1H),6.83(s,2H),6.49(s,1H),3.85(s,6H),3.80(s,2H),2.26–2.05(m,1H),1.06(d,J＝6.6Hz,6H)。
The preparation of embodiment 23:Z-2-(3,5-dimethoxy phenyl)-3-(the positive penta oxygen phenyl of 2-) vinyl cyanide 6w, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-n-pentyloxy phenyl aldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow needles by recrystallizing methanol, yield is 17.7%, and fusing point is 38-40 DEG C. 1HNMR(300MHz,CDCl 3):δ8.16(d,J＝7.9Hz,1H),7.99(s,1H),7.38(d,J＝7.6Hz,1H),7.03(d,J＝6.6Hz,1H),6.93(d,J＝8.2Hz,1H),6.83(s,2H),6.49(s,1H),4.04(d,J＝5.8Hz,2H),3.85(s,6H),1.84(s,2H),1.44(s,4H),0.94(d,J＝6.3Hz,3H)。
The preparation of embodiment 24:Z-2-(3,5-dimethoxy phenyl)-3-(the just own oxygen phenyl of 2-) vinyl cyanide 6x, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), the positive hexyloxybenzaldehyde of 0.01mol2-and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain light yellow needles by recrystallizing methanol, yield is 30.7%, and fusing point is 42-44 DEG C. 1HNMR(300MHz,CDCl 3):δ8.16(d,J＝7.6Hz,1H),7.99(s,1H),7.39(t,J＝7.6Hz,1H),7.05(t,J＝7.4Hz,1H),6.93(d,J＝8.2Hz,1H),6.83(s,2H),6.49(s,1H),4.03(t,J＝6.3Hz,2H),3.85(s,6H),1.89–1.76(m,2H),1.48(s,2H),1.34(s,4H),0.89(s,3H)。
The preparation of embodiment 25:Z-2-(3,5-dimethoxy phenyl)-3-(3-phenelyl) vinyl cyanide 6y, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol3-ethoxy-benzaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain off-white color solid by recrystallizing methanol, yield is 68.2%, and fusing point is 52-54 DEG C. 1HNMR(300MHz,CDCl 3):δ7.49(s,2H),7.36(d,J＝7.2Hz,2H),6.97(d,J＝7.0Hz,1H),6.80(d,J＝2.2Hz,2H),6.50(d,J＝2.1Hz,1H),4.10(q,J＝7.0Hz,2H),3.85(s,6H),1.45(t,J＝7.0Hz,3H)。
The preparation of embodiment 26:Z-2-(3,5-dimethoxy phenyl)-3-(2-thienyl) vinyl cyanide 7a, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol thiophene-2-formaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain yellow needle-like crystals by recrystallizing methanol, yield is 63.2%, and fusing point is 90-92 DEG C. 1HNMR(300MHz,CDCl 3):δ7.70–7.63(m,2H),7.55(d,J＝5.0Hz,1H),7.18–7.13(m,1H),6.77(d,J＝2.1Hz,2H),6.47(d,J＝2.0Hz,1H),3.84(s,6H)。13CNMR(75MHz,CDCl 3):δ161.19,160.92,142.33,136.96,131.32,126.17,118.56,114.85,108.31,104.07,100.78,63.71,55.53,14.72。IR(KBr)cm -1:2837(-OCH 3),2208(-CN),839(-C＝C-H)。MS-EI:m/z:271(M+1) +。
The preparation of embodiment 27:Z-2-(3,5-dimethoxy phenyl)-3-(2-furyl) vinyl cyanide 7b, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-furtural and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain black solid by recrystallizing methanol, yield is 56.8%, and fusing point is 46-48 DEG C. 1HNMR(300MHz,CDCl 3):δ7.60(d,J＝1.7Hz,1H),7.37(s,1H),7.21(d,J＝3.6Hz,1H),6.77(d,J＝2.2Hz,2H),6.60–6.56(m,1H),6.46(t,J＝2.1Hz,1H),3.84(s,6H)。
The preparation of embodiment 28:Z-2-(3,5-dimethoxy phenyl)-3-(2-pyridyl) vinyl cyanide 8, reaction equation is as follows:
Adopt the way of the similar synthetic mesophase product of embodiment 1, get 0.01mol3,5-dimethoxybenzeneacetonitrile (5), 0.01mol2-pyridylaldehyde and 20mL methyl alcohol are in 50mL there-necked flask, stirring is warming up to 60 DEG C, adds sodium methylate 0.005mol, isothermal reaction 4-6h, thin-layer chromatography tracing detection, be cooled to room temperature after question response, filter, washing, dry, obtain brown needle-like crystals by recrystallizing methanol, yield is 60.5%, and fusing point is 82-84 DEG C. 1HNMR(300MHz,CDCl 3):δ8.76(d,J＝4.0Hz,1H),7.98(d,J＝8.0Hz,1H),7.81(td,J＝7.7,1.7Hz,1H),7.64(s,1H),7.33(dd,J＝7.5,4.8Hz,1H),6.88(d,J＝2.2Hz,2H),6.52(t,J＝2.1Hz,1H),3.82(d,J＝14.5Hz,6H)。
Except these compounds, other series compounds can also be synthesized by same procedure, as a series of A ring be 3,4,5-trimethoxy phenyl ring, B ring 4-position-F ,-Cl ,-Br ,-N (CH 3) 2,-phenoxy group ,-OCH 3,-OC 2h 5,-OC 3h 8(just, different) ,-OC 4h 9(just, different) ,-OC 4h 9substituting groups such as (just, different) is replaced, or B ring replaces with thiphene ring, furan nucleus, pyrazole ring, the ethylene unit of piperazine ring etc. is introduced the Verakanol derivative of cyano group.
Embodiment 29: biological activity test
Experimental procedure is as follows:
1. cyano-containing resveratrol analogs, contrast medicine taxol (taxol), contrast medicine cis-platinum (PDD) are made into the storing solution of ultimate density 1000 times with DMSO, lucifuge freezen protective in gnotobasis, before use this storing solution substratum is diluted to the test liquid of 1000 times, for subsequent use;
2. before experiment by human colon cancer cell HCT116, human liver cancer cell BEL-7402 and human normal liver cell L 02 RPMI-1640 substratum (containing 10%FBS and 1% penicillin streptomycin dual anti-) cultivate, people's uterine cancer cells HeLa cell DMEM substratum (containing 10%FBS and 1% penicillin streptomycin dual anti-) cultivate;
3. HCT116, HeLa, BEL-7402 and L02 of taking the logarithm vegetative period are inoculated in 96 orifice plates with every hole 6000-8000 cell;
4. cultivate overnight after change the above-mentioned test liquid of different concns into, continue cultivation and discard substratum after 48 hours, substratum is discarded after continuing to cultivate 4h after every hole adds 0.1g/LMTT solution, its absorbance is surveyed at 492nm wavelength place, by following formulae discovery inhibiting rate after fully dissolving generated first a ceremonial jade-ladle, used in libation with DMSO.
Inhibiting rate %=[(1-experimental group absorbance)/control group absorbance] * 100%
Half-inhibition concentration (the IC of test compound to cell is calculated again according to inhibiting rate value 50), all experiments repeat more than 3 times under the same conditions, and net result represents with mean ± SD.
For the present invention, the cyano-containing resveratrol analogs of part of representative with contrast medicine taxol (taxol), cis-platinum (PDD), biological activity test result is as shown in the table:
As seen from table:
Introduce in the ethylene unit of cyano group, A ring is 3, the trans-resveratrol structure of 5-dimethoxy phenyl ring, 4, B ring has that oxyethyl group, propoxy-, isopropoxy, dimethylamino, chlorine, bromine, methyl, ethyl or B ring are heterocycle thienyl, furyl and pyridine base class have very strong antitumour activity to HCT116 human colon cancer cell.It is strong to BEL-7402 human hepatoma cell proliferation inhibit activities that 4, B ring has oxyethyl group, dimethylamino, chlorine to replace, but it is weak to the proliferation inhibition activity of human normal liver cell L 02, they are all to BEL-7402 human liver cancer cell and the selective restraining effect of human normal liver cell L 02
Above embodiment only in order to technical scheme of the present invention to be described, is not intended to limit; Although with reference to previous embodiment to invention has been detailed description, those of ordinary skill in the art is to be understood that: it still can be modified to the technical scheme described in foregoing embodiments, or carries out equivalent replacement to wherein portion of techniques feature; And these amendments or replacement, do not make the essence of appropriate technical solution depart from the spirit and scope of various embodiments of the present invention technical scheme.

Claims (7)

1. cyano-containing resveratrol analogs, is characterized in that, general structure is as follows:
In I, the R on phenyl ring is p-F, p-Cl, p-Br, o-Cl, o-Br, p-N (CH 3) 2, p-OBn, p-CH 3, p-CH 2cH 3, p-OCH 2cH 3, p-OCH 2cH 2cH 3, p-OCH (CH 3) 2, p-O (CH 2) 3cH 3, p-OCH 2cH (CH 3) 2, p-O (CH 2) 4cH 3, p-O (CH 2) 2cH (CH 3) 2, p-O (CH 2) 5cH 3, o-OCH 2cH 3, o-OCH 2cH 2cH 3, o-OCH (CH 3) 2, o-O (CH 2) 3cH 3, o-CH 2cH (CH 3) 2, o-O (CH 2) 4cH 3, o-O (CH 2) 5cH 3, m-OCH 2cH 3in any one.
2. cyano-containing resveratrol analogs as claimed in claim 1, it is characterized in that, another kind of structural formula is:
。
3. cyano-containing resveratrol analogs as claimed in claim 1, it is characterized in that, another kind of general structure is:
In III, X is any one in S, O.
4. a preparation method for cyano-containing resveratrol analogs as claimed any one in claims 1 to 3, it is characterized in that, synthesis step is as follows:
1. 3,5-resorcylic acid methyl-sulfates carry out methylation reaction, obtain 3,5-dimethoxy p-methyl;
2. 3,5-dimethoxy p-methyls obtain 3,5-3,5-dimethoxybenzoic alcohol by reduction reaction again;
3. 3,5-3,5-dimethoxybenzoic alcohols are at PBr 3dichloromethane solution in realize bromo and obtain 3,5-dimethoxy bromobenzyl;
4. use trimethylsilyl cyanide and tetrabutyl ammonium fluoride to introduce cyano group in the ethylene unit of 3,5-dimethoxy bromobenzyl, obtain 3,5-dimethoxybenzeneacetonitrile;
5. any one in 3,5-dimethoxybenzeneacetonitriles and aromatic aldehyde, substituted aroma aldehyde, pyridine aldehydes, Furan Aldehydes, thiophene aldehyde reacts and generates cyano-containing resveratrol analogs in methyl alcohol and sodium methylate.
5. the preparation method of cyano-containing resveratrol analogs as claimed in claim 4, is characterized in that, synthesis step 4. in, 3,5-dimethoxybenzyl bromide: trimethylsilyl cyanide: the add-on mol ratio of tetrabutyl ammonium fluoride is 0.01:0.015:0.015.
6. the purposes of a cyano-containing resveratrol analogs as claimed any one in claims 1 to 3.
7. cyano-containing resveratrol analogs as claimed in claim 6, is characterized in that, be applied to cancer therapy drug.
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