CN104031046A - N1-butyrylevodiamine and synthesis method thereof - Google Patents

N1-butyrylevodiamine and synthesis method thereof Download PDF

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CN104031046A
CN104031046A CN201410242065.7A CN201410242065A CN104031046A CN 104031046 A CN104031046 A CN 104031046A CN 201410242065 A CN201410242065 A CN 201410242065A CN 104031046 A CN104031046 A CN 104031046A
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evodiamine
butyryl
add
ethyl acetate
formula
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张景勍
胡雪原
孙立力
万坤
谭群友
何丹
张永红
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Chongqing Medical University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed systems

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

The invention belongs to the field of chemical synthesis of medicines and relates to a molecular structure of N1-butyrylevodiamine and a synthesis method thereof. The N1-butyrylevodiamine is prepared through the following steps: dissolving evodiamine in a solvent N,N-dimethylformamide, adding sodium hydride and stirring, adding butyryl chloride, continuously stirring after slowly increasing the temperature, adding purified water, extracting by using ethyl acetate, collecting an ethyl acetate extract, washing the extract by using the purified water and carrying out spin-drying to remove the solvent, taking a mixed solvent of petroleum ether and ethyl acetate as an eluting solution, separating by use of a silicagel column, and carrying out spin-drying to remove the solvent, thereby obtaining the N1-butyrylevodiamine.

Description

N 1-butyryl evodiamine and synthetic method
Technical field
The invention belongs to the synthetic field of pharmaceutical chemistry, relate to a kind of N 1the molecular structure of-butyryl evodiamine and synthetic method thereof.
Background technology
Evodiamine is from rutaceae Medcinal Evodia Fruit, dredge a kind of alkaloid extracting in the dry maturescent fruit of hair Medcinal Evodia Fruit or stone tiger, modern medicine study shows, evodiamine has vasodilation, anti-inflammatory, analgesia, temperature stomach antiemetic, warming spleen and stopping diarrha, rising body temperature, pharmacological action such as antitumor grade, there is wide DEVELOPMENT PROSPECT, but because evodiamine oral absorption is incomplete, the features such as bioavailability is low, limit its widespread use (Shyr MH clinically, Lin LC, Lin TY.Determination and pharmacokinetics of evodiamine in the plasma and feces of conscious rats.Analytica Chimica Acta, 2006, 558 (1/2): 16-21).Research report shows both at home and abroad, by the structure of modification to medicine and modification, can strengthen the restraining effect of medicine to tumour cell, improves the bioavailability of medicine.In recent years, investigator, by structural modification and transformation to evodiamine, has prepared multiple evodiamine derivative, in above-mentioned research, many by modifying evodiamine C 9, C 7, C 5site or N 13site, form evodiamine derivative (Dong GQ et al.Selection ofevodiamine as a novel topoisomerase I inhibitor by structure-based virtual screening and hit optimization of evodiamine derivatives as antitumor agents.J.Med.Chem.2010,53,7521-7531; Song S, Chen Z, Li S, Huang Y, Wan Y, Song H.Design, synthesis and evaluation of N13-substituted evodiamine derivatives against human cancer cell lines.Molecules.2013,18 (12): 15750-15768).The present invention is taking evodiamine as primer, adopts the method for one-step synthesis, by N 1the structural modification of position, synthetic N 1-butyryl evodiamine, to improve bioavailability.Through inquiry patent and document, there is no at present by evodiamine N 1position is carried out Butyrylation and is modified synthetic N 1any research report of-butyryl evodiamine.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of N that can improve drug bioavailability that has 1-butyryl evodiamine and preparation method thereof.The N that the present invention obtains 1-butyryl evodiamine and evodiamine comparison, have oral absorption good, the advantage that bioavailability is high, and N 1the synthesis technique of-butyryl evodiamine is simple, environmental protection, and cost is lower, is easy to control, and is easy to suitability for industrialized production.
N provided by the invention 1-butyryl evodiamine (14-tetrahydrochysene-7H-indoles is [2 ' 3 ': 3,4] pyrido [2,1-b] quinazoline-5-ketone also for 1-butyryl radicals-14-methyl-8,13,13b), is characterized in that its structural formula is suc as formula (I):
Technical scheme of the present invention is: taking evodiamine as raw material, the structure of evodiamine is shown in formula (II), be dissolved in N, in the solvent of dinethylformamide, add sodium hydride to stir after 0.5 hour, add n-butyryl chloride, the structure of n-butyryl chloride is shown in formula (III), and the temperature to 80 that slowly raises DEG C continued to stir after 24 hours, add water, be extracted with ethyl acetate 3 times, combining extraction liquid, washes after three times, rotary evaporation is except desolventizing, taking the mixed solution of sherwood oil and ethyl acetate as eluent, use silicagel column separation and purification, obtain light green solid chemical compound N 1-butyryl evodiamine, is shown in formula (I).
Reaction formula of the present invention is:
N provided by the invention 1the preparation method of-butyryl evodiamine, it is characterized in that the method comprises the following steps: structural formula to be dissolved in N suc as formula the evodiamine of (II), in dinethylformamide solvent, after adding sodium hydride to stir, add the n-butyryl chloride of structural formula suc as formula (III), slowly after rising temperature, continue to stir, add purified water, be extracted with ethyl acetate, extraction liquid is with being spin-dried for solvent after purified water washing, taking the mixed solution of sherwood oil and ethyl acetate as eluent, silicagel column separates, rotary evaporation is except desolventizing, obtain light green solid chemical compound, be the N of structural formula suc as formula (I) 1-butyryl evodiamine, reaction process is as follows:
N 1the preparation method of-butyryl evodiamine, is characterized in that: temperature of reaction is 70-90 DEG C, and the reaction times is 18-36 hour, and the mol ratio of evodiamine and sodium hydride is 1: 5～1: 12, and described evodiamine and the mol ratio of n-butyryl chloride are 1: 3～1: 6.
The present invention is characterised in that in synthetic preparation: 1) taking DMF as solvent, overcome the poorly soluble shortcoming of evodiamine; 2) to choose sodium hydride be catalyzer in the present invention, and aftertreatment is easy; 3) temperature of reaction of the present invention should be controlled between 70-90 DEG C, and the reaction times is 18-36 hour, and temperature of reaction and reaction times that claim limits are the temperature and time that this reaction yield is higher; 4) mol ratio of described evodiamine and sodium hydride is 1: 5～1: 12, and now, productive rate is higher; 5) described evodiamine and n-butyryl chloride molar ratio be 1: 3～1: 6, now, can obtain higher productive rate, avoid waste or reaction yield low.
The N making with the present invention 1-butyryl evodiamine, the qualification result of mass spectrum MS is shown in Fig. 1, as can be seen from Figure 1 N 1the molecular weight of-butyryl evodiamine is 373.Hydrogen nuclear magnetic resonance 1the qualification result of H-NMR is shown in Fig. 2, as can be seen from Figure 2, and HNMR (CDCl 3, 400MHz) and δ 1.02 (q, 3H), 1.87 (m, 2H), 2.36 (s, 3H), 2.89-3.25 (m, 5H), 5.0 (dd, 1H), 6.28 (s, 1H), 7.08-7.58 (m, 6H), 8.10-8.16 (m, 2H).From MS and 1h-NMR qualification result shows to have obtained N 1-butyryl evodiamine.
After Oral Administration in Rats administration, in body, pharmacokinetics investigation result shows, with respect to evodiamine, and N 1in the body of-butyryl evodiamine, clearance rate reduces, and area under the drug-time curve increases, and peak concentration Cmax increases, N 1-butyryl evodiamine can improve absorption, and bioavailability in vivo obviously increases.Male SD rat gastric infusion N 1-butyryl evodiamine or evodiamine, dosage is 100mg/kg.Get blood respectively at different time eye socket rear vein beard after administration, be placed in heparinization test tube, mix, centrifugal (12000r/min) 5min, separates upper plasma, in-20 DEG C of refrigerators, saves backup.Plasma sample treatment process is: draw 150 μ L plasma samples, add mark working fluid Honokiol in 10 μ L, vortex 30s, adds ammoniacal liquor, after vortex 30s, adds ether, vortex 3min; The centrifugal 5min of 4000rpm, get supernatant liquor to centrifuge tube, 40 DEG C of water-baths volatilize after ether, add methyl alcohol, vortex 1min, the centrifugal 10min of 12000rpm, getting 20u L supernatant liquor adopts high-efficient liquid phase technique marker method to detect, result substitution regression equation calculation Plasma Concentration, curve while obtaining medicine, is shown in Fig. 3.
Brief description of the drawings
Fig. 1 is the N that the present invention makes 1the qualification result of the mass spectrum MS of-butyryl evodiamine.N as can be seen from Figure 1 1the molecular weight of-butyryl evodiamine is 373.
Fig. 2 is the N that the present invention makes 1the hydrogen nuclear magnetic resonance of-butyryl evodiamine 1the qualification result of H-NMR.As can be seen from Figure 2, HNMR (CDCl 3, 400MHz) and δ 1.02 (q, 3H), 1.87 (m, 2H), 2.36 (s, 3H), 2.89-3.25 (m, 5H), 5.0 (dd, 1H), 6.28 (s, 1H), 7.08-7.58 (m, 6H), 8.10-8.16 (m, 2H).
Fig. 3 is the N that the present invention makes 1graphic representation when medicine in body after the Oral Administration in Rats administration of-butyryl evodiamine.Ordinate zou is drug level, and X-coordinate is the time.
Embodiment
In order to further illustrate the present invention and advantage thereof, provide following specific embodiment, should understand that these embodiment only limit to illustrate instead of as the restriction of the scope of the invention.
Embodiment 1:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.1323g (now, the mol ratio of evodiamine and sodium hydride is 1: 5), after magnetic agitation 0.5h, add (20 DEG C of 0.136mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 2), the temperature to 70 DEG C that slowly raises, magnetic agitation 18h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.
Embodiment 2:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.2630g (now, the mol ratio of evodiamine and sodium hydride is 1: 10), after magnetic agitation 0.5h, add (20 DEG C of 0.35mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 5), the temperature to 80 DEG C that slowly raises, magnetic agitation 24h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), rotary evaporation is except desolventizing, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, is spin-dried for solvent, obtains light green N 1-butyryl evodiamine (formula I) solid 137mg, yield 55.64%, purity > 97%.
Embodiment 3:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.1323g (now, the mol ratio of evodiamine and sodium hydride is 1: 5), after magnetic agitation 0.5h, add (20 DEG C of 0.401mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 6), the temperature to 70 DEG C that slowly raises, magnetic agitation 18h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nn fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.
Embodiment 4:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.3181g (now, the mol ratio of evodiamine and sodium hydride is 1: 12), after magnetic agitation 0.5h, add (20 DEG C of 0.401mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 6), the temperature to 70 DEG C that slowly raises, magnetic agitation 18h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40rnL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.
Embodiment 5:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, N solvent dimethylformamide, ultrasonic dissolution, add sodium hydride (60%) 0.1323g (now, the mol ratio of evodiamine and sodium hydride is 1: 5), after magnetic agitation 0.5h, add (20 DEG C of 0.136mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 2), the temperature to 70 DEG C that slowly raises, magnetic agitation 36h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.
Embodiment 6:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.1323g (now, the mol ratio of evodiamine and sodium hydride is 1: 5), after magnetic agitation 0.5h, add (20 DEG C of 0.401mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 6), the temperature to 70 DEG C that slowly raises, magnetic agitation 36h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.
Embodiment 7:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.1323g (now, the mol ratio of evodiamine and sodium hydride is 1: 5), after magnetic agitation 0.5h, add (20 DEG C of 0.136mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 2), the temperature to 90 DEG C that slowly raises, magnetic agitation 18h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.
Embodiment 8:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.3181g (now, the mol ratio of evodiamine and sodium hydride is 1: 12), after magnetic agitation 0.5h, add (20 DEG C of 0.136mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 2), the temperature to 90 DEG C that slowly raises, magnetic agitation 18h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.
Embodiment 9:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.1323g (now, the mol ratio of evodiamine and sodium hydride is 1: 5), after magnetic agitation 0.5h, add (20 DEG C of 0.136mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 2), the temperature to 90 DEG C that slowly raises, magnetic agitation 36h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.
Embodiment 10:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.1323g (now, the mol ratio of evodiamine and sodium hydride is 1: 5), after magnetic agitation 0.5h, add (20 DEG C of 0.401mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 6), the temperature to 90 DEG C that slowly raises, magnetic agitation 36h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.
Embodiment 11:
Take evodiamine (formula II) 0.2g and be placed in 50ml round-bottomed flask, add the N of 15mL, dinethylformamide solvent, ultrasonic dissolution, add sodium hydride (60%) 0.3181g (now, the mol ratio of evodiamine and sodium hydride is 1: 12), after magnetic agitation 0.5h, add (20 DEG C of 0.136mL; Density is 1.03g/mL) n-butyryl chloride (formula III) (now, the mol ratio of evodiamine and n-butyryl chloride is 1: 2), the temperature to 90 DEG C that slowly raises, magnetic agitation 36h, termination reaction; In reaction solution, add 40mL purified water, be placed to room temperature, add ethyl acetate extraction 3 times (each 40mL), collect upper layer of extraction liquid, add after purified water washing 3 times (each 50mL), be spin-dried for solvent, taking ethyl acetate: sherwood oil volume ratio is as the solution of 1: 4 is as elutriant, utilize silicagel column to separate, point sample on silica gel G 250 thin layer plates, taking hexanaphthene: ethyl acetate: methyl alcohol: triethylamine (19: 5: 1: 1) as developping agent, taking 10% ethanol solution of sulfuric acid as developer, colour developing under 365nm fluorescence irradiates, collects R fvalue is 0.47 solution, and rotary evaporation, except desolventizing, obtains light green N 1-butyryl evodiamine (formula I) solid.

Claims (3)

1. a N 1-butyryl evodiamine (14-tetrahydrochysene-7H-indoles is [2 ' 3 ': 3,4] pyrido [2,1-b] quinazoline-5-ketone also for 1-butyryl radicals-14-methyl-8,13,13b), is characterized in that its structural formula is suc as formula (I), and molecular weight is 373:
。
2. N according to claim 1 1the preparation method of-butyryl evodiamine, it is characterized in that the method comprises the following steps: structural formula to be dissolved in N suc as formula the evodiamine of (II), in dinethylformamide solvent, after adding sodium hydride to stir, add the n-butyryl chloride of structural formula suc as formula (III), slowly after rising temperature, continue to stir, add purified water, be extracted with ethyl acetate, collect acetic acid ethyl acetate extract, with being spin-dried for solvent after purified water water washing, taking the mixed solvent of sherwood oil and ethyl acetate as elute soln, silicagel column separates, be spin-dried for solvent, obtain the evodiamine Butyrylation derivative of structural formula suc as formula (I), reaction process is as follows:
。
3. N according to claim 2 1the preparation method of-butyryl evodiamine, is characterized in that: temperature of reaction is 70-90 DEG C, and the reaction times is 18-36 hour, and the mol ratio of evodiamine and sodium hydride is 1: 5～1: 12, and described evodiamine and the mol ratio of n-butyryl chloride are 1: 3～1: 6.
CN201410242065.7A 2014-05-26 2014-05-26 N1-butyrylevodiamine and synthesis method thereof Pending CN104031046A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110483550A (en) * 2019-09-04 2019-11-22 南华大学 One kind derivative of rutaecarpin containing trimethoxyphenyl and its application

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Publication number Priority date Publication date Assignee Title
CN101787025A (en) * 2010-03-04 2010-07-28 中国人民解放军第二军医大学 Substituted-evodiamine anti-tumor and antifungal compounds and preparation method thereof
WO2012126280A1 (en) * 2011-03-21 2012-09-27 中国医学科学院医药生物技术研究所 Rutaecarpine compound, preparation method therefor, and use thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101787025A (en) * 2010-03-04 2010-07-28 中国人民解放军第二军医大学 Substituted-evodiamine anti-tumor and antifungal compounds and preparation method thereof
WO2012126280A1 (en) * 2011-03-21 2012-09-27 中国医学科学院医药生物技术研究所 Rutaecarpine compound, preparation method therefor, and use thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110483550A (en) * 2019-09-04 2019-11-22 南华大学 One kind derivative of rutaecarpin containing trimethoxyphenyl and its application

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Application publication date: 20140910