CN107353219A - A kind of macamide compound and its synthetic method, application - Google Patents

A kind of macamide compound and its synthetic method, application Download PDF

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Publication number
CN107353219A
CN107353219A CN201710609418.6A CN201710609418A CN107353219A CN 107353219 A CN107353219 A CN 107353219A CN 201710609418 A CN201710609418 A CN 201710609418A CN 107353219 A CN107353219 A CN 107353219A
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macamide
synthetic method
compound
benzyl
maca
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夏陈
陈建
邓俊琳
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Saas Agro-Food Science & Technology Research Institute
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Saas Agro-Food Science & Technology Research Institute
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/373—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in doubly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
    • C07C235/76—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton

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  • Organic Chemistry (AREA)
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  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)

Abstract

The present invention relates to drug field, in particular to a kind of macamide compound and its synthetic method, application.A kind of macamide synthetic method, it includes：Linoleic acid obtains maca ene mixture with oxidant by pyridine derivate catalysis oxidation；Chromatographic isolation is prepared by being used after maca ene mixture and benzylamine or benzyl amine derivative amidation process；Wherein：Oxidant is any of 2,2,6,6 tetramethyl piperidine nitrogen oxides, pyridinium tribromide, 2 iodosobenzoic acids；Benzyl amine derivative is 3 methoxybenzyl ammonia or 3,4 dimethoxy benzyl ammonia.The present invention is synthesized by initial reactant of linoleic acid, compared to of the prior art for plant Maca extracts macamide, required low in raw material price, is easy to get；In addition, simple to operate during synthetically prepared, accessory substance is few, required reagent, solvent small toxicity and be easy to get.New route is provided for a large amount of preparations of macamide monomeric compound.

Description

A kind of macamide compound and its synthetic method, application
Technical field
The present invention relates to drug field, in particular to a kind of macamide compound and its synthetic method, application.
Background technology
Maca (Lepidium meyenii Walp.) is Cruciferae separate row Vegetable spp (Lepidium L.).Life in 1 year or 2 Year raw herbaceous plant, the andes region originated in more than Peru height above sea level 3500m can be grown in and its rugged environment.Maca Rich in nutritional ingredients such as protein, amino acid, polysaccharide, dietary fiber, vitamin, mineral matters, and glucosinolate, maca ene and A variety of secondary metabolites such as macamide, wherein macamide are exclusive for maca.Maca is nutritious, has and improves life Educate power, improve the multiple efficacies such as sexual function, antifatigue, anti-osteoporosis, anti-oxidant, anticancer and protection nerve.With people couple The bioactivity of macamide class material and functional health application study, the preparation to macamide class monomeric compound have weight Big meaning.
At present, it is to use plant Maca to carry out active component for raw material that the extracting method of plant Maca composition, which is mainly reported, Extraction, but currently without a large amount of synthetic methods of macamide monomeric compound.
The content of the invention
It is an object of the invention to provide a kind of macamide compound and its synthetic method, application, and it is intended to improve now The problem of some macamide monomeric compounds can not be prepared largely.
The present invention provides a kind of technical scheme：
A kind of macamide synthetic method, it includes：Linoleic acid is obtained with oxidant by pyridine derivate catalysis oxidation Maca ene mixture；Maca ene mixture is separated with after benzylamine or benzyl amine derivative amidation process with preparative chromatography；
Wherein：Oxidant is 2, in 2,6,6- tetramethyl piperidines-nitrogen-oxide, pyridinium tribromide, 2- iodosobenzoic acids It is any.Benzyl amine derivative is any of 3- methoxybenzyls ammonia, 3,4- dimethoxy benzyl ammonia.
Further, above-mentioned linoleic acid and the reaction dissolvent of oxidant reaction are DMF, acetonitrile, dichloro Any of methane and dimethyl sulfoxide (DMSO).
Further, above-mentioned pyridine derivate is DMAP, 4- pyrollidinopyridines and 2,6- dimethyl Any of pyridine.
Further, above-mentioned linoleic acid and oxidant be by pyridine derivate catalytic oxidation, including：To dissolved with sub- oil Acid solvent in add pyridine derivate reaction after, remove solvent, with dichloromethane dissolve residue, with unsaturated carbonate sodium salt, Water washing, dichloromethane is removed, obtains maca ene mixture.
Further, the condensation reagent of above-mentioned maca ene mixture and benzylamine amidation process is N, N'- cyclohexyl carbon two Imines, N, N'- DICs, 1- ethyls-(3- dimethylaminopropyls) phosphinylidyne diimmonium salt hydrochlorate, 2- (7- oxygen Change BTA)-N, N, N ', N '-tetramethylurea hexafluorophosphoric acid ester, hexafluorophosphoric acid BTA -1- bases-epoxide tripyrrole alkane Any of base phosphorus, N, ' N- carbonyl dimidazoles.
Further, the solvent of above-mentioned maca ene mixture and benzylamine amidation process be selected from DMF, Any of dichloromethane and dimethyl sulfoxide (DMSO).
Further, after above-mentioned maca ene mixture and the benzylamine amidation process, in addition to：Use saturated sodium carbonate Reactant mixture after aqueous salt solu-tion amidation process, concentration remove the reaction reagent of amidation process.
Further, above-mentioned with preparing in chromatrographic separation step, mobile phase is that volume ratio is 70-75:25 organic solvent With water；Organic solvent is that 0.01-0.02%vol trifluoroacetic acid-acetonitrile solution, 0.01-0.02%vol acetate-methanol are molten Any of formic acid-propanol solution of liquid, 0.01-0.02%vol；The absorbing wavelength is being taken to be in chromatrographic separation step with preparing 280nm product.
A kind of macamide compound, it is synthesized by above-mentioned macamide synthetic method；
Macamide compound is：N- benzyl -13- carbonyls -9 (Z), 11 (E)-ten eight carbon diene amide；N- benzyl -9- carbonyls Base -10 (E), 12 (Z)-ten eight carbon diene amide；N- benzyl -9- carbonyls -10 (E), in 12 (E)-ten eight carbon diene amide extremely Few one kind.
Application of the above-mentioned macamide compound in preparing antifatigue, anti-senile dementia and improving sexual function medicine.
Macamide compound and its synthetic method provided in an embodiment of the present invention, the beneficial effect of application are：
The synthetic method of macamide compound provided by the invention can synthesize macamide monomer, using linoleic acid as rise Beginning raw material is synthesized, compared to of the prior art for plant Maca extracts macamide, required cost of material It is low in cost and easily available；In addition, simple to operate during synthetically prepared, accessory substance is few, required reagent, solvent small toxicity and It is easy to get.Reduce the preparation cost of macamide compound.New road is provided for a large amount of preparations of macamide monomeric compound Line.
Brief description of the drawings
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below by embodiment it is required use it is attached Figure is briefly described, it will be appreciated that the following drawings illustrate only certain embodiments of the present invention, therefore be not construed as pair The restriction of scope, for those of ordinary skill in the art, on the premise of not paying creative work, can also be according to this A little accompanying drawings obtain other related accompanying drawings.
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of compound one in the synthetic product of the embodiment of the present invention 1；
Fig. 2 is the carbon-13 nmr spectra figure of compound one in the synthetic product of the embodiment of the present invention 1；
Fig. 3 is the hydrogen nuclear magnetic resonance spectrogram of compound two in the synthetic product of the embodiment of the present invention 1；
Fig. 4 is the carbon-13 nmr spectra figure of compound two in the synthetic product of the embodiment of the present invention 1；
Fig. 5 is the hydrogen nuclear magnetic resonance spectrogram of compound three in the synthetic product of the embodiment of the present invention 1；
Fig. 6 is the carbon-13 nmr spectra figure of compound three in the synthetic product of the embodiment of the present invention 1.
Embodiment
, below will be in the embodiment of the present invention to make the purpose, technical scheme and advantage of the embodiment of the present invention clearer Technical scheme be clearly and completely described.Unreceipted actual conditions person, builds according to normal condition or manufacturer in embodiment The condition of view is carried out.Agents useful for same or the unreceipted production firm person of instrument, it is the conventional production that can be obtained by commercially available purchase Product.
Below the macamide compound and its synthetic method to the embodiment of the present invention, using being specifically described.
A kind of macamide synthetic method, it includes：Linoleic acid is obtained with oxidant by pyridine derivate catalysis oxidation Maca ene mixture；Chromatographic isolation is prepared by being used after maca ene mixture and benzylamine or benzyl amine derivative amidation process；
Wherein：Oxidant is 2, in 2,6,6- tetramethyl piperidines-nitrogen-oxide, pyridinium tribromide, 2- iodosobenzoic acids It is any.Benzyl amine derivative is 3- methoxybenzyls ammonia or 3,4- dimethoxy benzyl ammonia.
Linoleic acid, molecular formula：CH3(CH2)4CH=CHCH2CH=CH (CH2)7COOH；One kind of unrighted acid, nothing Color is to weak yellow liquid, ingress of air changeable colour.
TEMPO, tetramethyl piperidine nitrogen oxides；2,2,6,6- tetramethyl piperidines-nitrogen-oxide；English name：2,2,6,6- Tetramethyl-1-piperidinyloxy；Molecular formula：C9H18NO。
Py.HBr3 pyridinium tribromides；English name：pyridinium hydrobromide perbromide；Molecular formula： C5H6Br3N.IBX, 2- iodosobenzoic acid (2-Iodoxybenzoic acid), molecular formula：C7H5IO4。
With oxidant oxidation reaction occurs under pyridine derivate catalyst action for linoleic acid, generates maca ene mixture； Further, contain in maca ene mixture：13- carbonyls -9 (Z), 11 (E)-octadecadienoic acids；Structural formula is as follows：
9- carbonyls -10 (E), 12 (Z)-octadecadienoic acids；Structural formula is as follows：
9- carbonyls -10 (E), 12 (E)-octadecadienoic acids；Structural formula is as follows：
Further, during linoleic acid obtains maca ene mixture with TEMPO by pyridine derivate catalytic reaction, Above-mentioned pyridine derivate can be any in DMAP, 4- pyrollidinopyridines and 2,6- lutidines Kind.
Further, above-mentioned linoleic acid and the reaction dissolvent of oxidant reaction are DMF, acetonitrile, dichloro Any of methane and dimethyl sulfoxide (DMSO).
In the present embodiment, to dissolved with pyridine reaction is added in linoleic reaction dissolvent solution, reaction dissolvent is removed, is used Dichloromethane dissolves residue, is washed with unsaturated carbonate natrium brine, removes dichloromethane, obtains maca ene mixture.
Specifically, weigh 1g linoleic acid (purity 95%) and be dissolved in 20ml acetonitriles, add 0.5g4- dimethylamino naphthyridines (DMAP) 1.6g (TEMPO), is added, reacts 4h, 30 DEG C of removing acetonitriles that are concentrated under reduced pressure, residue 20ml dichloromethane at room temperature Dissolving, is washed with 10ml saturated aqueous sodium carbonates, and 30 DEG C of removing dichloromethane that are concentrated under reduced pressure, obtain maca ene and mix after washing 3 times Compound.
Further, above-mentioned saturated aqueous sodium carbonate is alternatively saturated sodium bicarbonate, 10% sodium chloride etc..
Above-mentioned maca ene mixture carries out amidation process with benzylamine or benzyl amine derivative, will be mixed after amidation process Product is closed to be separated with chromatography is prepared.Benzyl amine derivative is 3- methoxybenzyls ammonia or 3,4- dimethoxy benzyl ammonia.
In other words, maca ene mixture can carry out amidatioon with benzylamine ,-methoxybenzyl ammonia or 3,4- dimethoxy benzyl ammonia Reaction.
Further, the condensation reagent of above-mentioned maca ene mixture and benzylamine amidation process is N, N'- cyclohexyl carbon two Imines, N, N'- DICs, 1- ethyls-(3- dimethylaminopropyls) phosphinylidyne diimmonium salt hydrochlorate, 2- (7- oxygen Change BTA)-N, N, N ', N '-tetramethylurea hexafluorophosphoric acid ester, hexafluorophosphoric acid BTA -1- bases-epoxide tripyrrole alkane Any of base phosphorus, N, ' N- carbonyl dimidazoles.
N, N'- carbodicyclo hexylimide：NN'Dicyclohexylcarbodie (DCC), molecular formula：C6H11N=C= NC6H11
N, ' N- carbonyl dimidazoles：Also known as 1,1'- carbonyl dimidazoles, 1,1'- N,N'-carbonyldiimidazoles and carbonyl dimidazoles；Molecular formula： C7H6N4O。
EDCI：1- ethyls-(3- dimethylaminopropyls) phosphinylidyne diimmonium salt hydrochlorate (EDC.HCL)；English name：1- Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride；Molecular formula：C8H17N3.HCl。
HATU：2- (7- aoxidizes BTA)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters；1-[Bis (dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate；Molecular formula：C10H15OF6N6P。
PyBOP：Hexafluorophosphoric acid BTA -1- bases-epoxide tripyrrole alkyl phosphorus；Molecular formula：C18H28F6N6OP2。
Further, maca ene mixture is carried out in amidation process with benzylamine, and amidated reaction dissolvent is selected from N, N- Any of dimethylformamide, dichloromethane and dimethyl sulfoxide (DMSO)；The catalyst of amidation process is selected from pyridine, 4- bis- Any of methylamino pyridine and 4- pyrollidinopyridines.
Specifically, take 0.03mol benzylamines, 0.02mol maca ene mixtures dissolve in 50m1 drying dichloromethane, After 0.03mol dimethylamino naphthyridines catalyst stirring 20min, add after dehydrating condensation agent (such as 0.02mol DCC) at room temperature Stirring reaction 3h, filtering, filtrate are washed 3 times repeatedly with saturated sodium carbonate solution, water successively, and organic phase is concentrated under reduced pressure in 30 DEG C and removed Remove dichloromethane.By the preparation chromatographic isolation of the product after concentration.
Further, above-mentioned with preparing in chromatrographic separation step, mobile phase is that volume ratio is 70-75:25 organic solvent With water.Further, organic solvent is 0.01-0.02%vol trifluoroacetic acid-acetonitrile solution, 0.01-0.02%vol second Any of formic acid-propanol solution of acid-methanol solution, 0.01-0.02%vol.
It should be noted that in other embodiments of the invention, mobile phase is alternatively other solution, such as other are organic Solution formic acid-propyl alcohol of acid and alcohol.
The product that absorbing wavelength is 280nm is being taken with preparation chromatrographic separation step.Mobile phase is that volume ratio is 75:25 Organic solvent and water；Organic solvent is 0.01-0.02%vol trifluoroacetic acid-acetonitrile solution.
Correspondingly, the reaction equation of above-mentioned each maca ene compound is as follows：
R1=H, R2=H
R1=H, R2=CH3-O-
R1=CH3- O-, R2=CH3-O-
The synthetic method of macamide compound provided by the invention can synthesize macamide monomer, with linoleic acid, TEMPO is that reactant is synthesized, for plant Maca in the prior art extracts macamide, required raw material valency Lattice are low in cost and easily available；In addition, simple to operate during synthetically prepared, accessory substance is few, required reagent, the small toxicity of solvent And it is easy to get.Reduce the preparation cost of macamide compound.There is provided newly for a large amount of preparations of macamide monomeric compound Route.
The present invention provides a kind of technical scheme：
A kind of macamide compound, synthesized by above-mentioned macamide synthetic method.
Further, above-mentioned macamide compound is：N- benzyl -13- carbonyls -9 (Z), 11 (E)-ten eight carbon diene acyl Amine；N- benzyl -9- carbonyls -10 (E), 12 (Z)-ten eight carbon diene amide；N- benzyl -9- carbonyls -10 (E), 12 (E)-ten eight carbon At least one of diene amide.
The present invention also provides a kind of technical scheme：
Application of the above-mentioned macamide compound in preparing antifatigue, anti-senile dementia and improving sexual function medicine.
The feature and performance of the present invention are described in further detail with reference to embodiments.
Embodiment 1
The present embodiment provides a kind of macamide compound, and the macamide compound is synthesized to obtain by following steps：
Weigh 1g linoleic acid and be dissolved in 20ml acetonitriles, add 0.5g DMAPs (DMAP) and be used as catalyst, then add Enter 1.6g TEMPO, react 4h at room temperature, be concentrated under reduced pressure in 30 DEG C and remove acetonitrile, residue 20ml dichloromethane dissolves, filtrate Washed repeatedly 3 times with saturated sodium carbonate solution, water successively, 30 DEG C of removing dichloromethane that are concentrated under reduced pressure, obtain maca ene mixture.
Take the above-mentioned maca ene mixture of 0.03mol benzylamines, 0.02mol to add the dichloromethane that 50m1 is dried, add 0.03mol DMAPs, stir 20min；0.03mol N are added, N'- carbodicyclo hexylimides, are stirred at room temperature React 3h, filtering；Filtrate is washed 3 times repeatedly with saturated sodium carbonate solution, water successively, takes 30 DEG C of organic phase to be concentrated under reduced pressure removing two Chloromethanes.Being separated using performance liquid chromatographic column, mobile phase is 0.01%vol trifluoroacetic acid-second eyeball, water, both Ratio is：75:25.Collect the product that absorbing wavelength is 280nm.
Embodiment 2
The present embodiment provides a kind of macamide compound, and the macamide compound is synthesized to obtain by following steps：
Weigh 1g linoleic acid and be dissolved in 20ml acetonitriles, add 0.5g 4- pyrollidinopyridines as catalyst, add 1.6g TEMPO, 4h being reacted at room temperature, being concentrated under reduced pressure in 30 DEG C and remove acetonitrile, residue 20ml dichloromethane dissolves, and filtrate is successively with full Washed repeatedly 3 times with sodium carbonate liquor, water, 30 DEG C of removing dichloromethane that are concentrated under reduced pressure, obtain maca ene mixture.
0.03mol 3 is taken, the above-mentioned maca ene mixture of 4- dimethoxy benzyls ammonia, 0.02mol adds the dichloro that 50m1 is dried Methane, 0.03mol 4- pyrollidinopyridines are added, stir 20min；0.03mol N are added, N'- dicyclohexyls carbon two is sub- Amine, stirring reaction 3h, is filtered at room temperature；Filtrate is washed 3 times repeatedly with saturated sodium carbonate solution, water successively, takes 30 DEG C of organic phase It is concentrated under reduced pressure and removes dichloromethane.Using prepare chromatogram separated, mobile phase be 0.01%vol trifluoroacetic acid-second eyeball, Water, both ratios are：75:25.Collect the product that absorbing wavelength is 280nm.
Embodiment 3
The present embodiment provides a kind of macamide compound, and the macamide compound is synthesized to obtain by following steps：
Weigh 1g linoleic acid and be dissolved in 20ml acetonitriles, add 0.5g 2,6- lutidines adds 1.6g as catalyst TEMPO, 4h being reacted at room temperature, being concentrated under reduced pressure in 30 DEG C and remove acetonitrile, residue 20ml dichloromethane dissolves, with 10ml saturation chlorine Change sodium water solution washing, wash 3 times, 30 DEG C of removing dichloromethane that are concentrated under reduced pressure, obtain maca ene mixture.
The above-mentioned maca ene mixture of 0.03mol 3- methoxybenzyls ammonia, 0.02mol is taken to add the dimethyl sulfoxide that 50m1 is dried, 0.03mol 2 is added, 6- lutidines, stirs 20min；Add 0.03mol N, N'- dicyclohexylcarbodiimides, room temperature Lower stirring reaction 3h, filtrate are washed 3 times repeatedly with saturated sodium carbonate solution, water successively, take 30 DEG C of organic phase to be concentrated under reduced pressure removing Dimethyl sulfoxide.Being separated using performance liquid chromatographic column, mobile phase is 0.02%vol trifluoroacetic acid-acetonitrile solution, water, Both ratio is：75:25.Collect the product that absorbing wavelength is 280nm.
Embodiment 4
The present embodiment provides a kind of macamide compound, and the macamide compound is synthesized to obtain by following steps：
Weigh 1g linoleic acid and be dissolved in 20ml acetonitriles, add 0.5g 4- pyrollidinopyridines as catalyst, add 1.6g TEMPO, 4h being reacted at room temperature, being concentrated under reduced pressure in 35 DEG C and remove acetonitrile, residue 20ml dichloromethane dissolves, and filtrate is used successively 10% sodium chloride solution, water wash 3 times repeatedly, 35 DEG C of removing dichloromethane that are concentrated under reduced pressure, obtain maca ene mixture.
The above-mentioned maca ene mixture of 0.03mol benzylamines, 0.02mol is taken to add the DMF that 50m1 is dried, 0.03mol DMAPs are added, stir 20min；Add 0.03mol N, N'- dicyclohexylcarbodiimides, room temperature Lower stirring reaction 3h, filtering；Filtrate is washed 3 times repeatedly with 10% sodium chloride solution, water successively, takes organic phase to be concentrated under reduced pressure removing DMF.Separated using performance liquid chromatographic column, mobile phase be 0.01%vol formic acid-propanol solution, Water, both ratios are：75:25.Collect the product that absorbing wavelength is 280nm.
Embodiment 5
The present embodiment provides a kind of macamide compound, and the macamide compound is synthesized to obtain by following steps：
Weigh 1g linoleic acid and be dissolved in 20ml acetonitriles, add 0.5g 4- pyrollidinopyridines as catalyst, add 1.6g TEMPO, 4h is reacted at room temperature, concentration removes acetonitrile, and residue 20ml dichloromethane dissolves, and filtrate is molten with saturated sodium carbonate successively Liquid, water wash 3 times repeatedly, and concentration removes dichloromethane, obtains maca ene mixture.
The above-mentioned maca ene mixture of 0.03mol benzylamines, 0.02mol is taken to add the DMF that 50m1 is dried, 0.03mol 4- pyrollidinopyridines are added, stir 20min；Add 0.03mol N, N'- dicyclohexylcarbodiimides, room temperature Lower stirring reaction 3h, filtering；Filtrate is washed 3 times repeatedly with saturated sodium carbonate solution, water successively, takes organic phase concentration to remove N, N- Dimethylformamide.Being separated using with preparation chromatogram, mobile phase is 0.02%vol acetate-methanol solution, water, both Ratio be：75:20.Collect the product that absorbing wavelength is 280nm.
Experimental example 1
To the macamide compound obtained in embodiment 1, recrystallize, obtain after collecting the product that absorbing wavelength is 280nm To three kinds of materials；Three kinds of materials are detected：Detection obtains the 34mg of compound one；The 218mg of compound two, compound three 277mg。
The wave spectrum of compound one/spectral detection result is as follows：
It is infrared：Peak value is Vmax=3285 (N-H), 2926,2850,1681 (C=O), 1630 (C=O), 1593,1551, 1456,1235,994,723,693cm-1；
Mass spectrum：m/z：384.29([M+H]+)；
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of compound one in the synthetic product of the embodiment of the present invention 1；Fig. 2 is implemented for the present invention The carbon-13 nmr spectra figure of compound one in the synthetic product of example 1.
Thus, it is possible to there is N- benzyl -9- carbonyls -10 (E), 12 (E)-ten eight carbon in confirming the product that embodiment 1 obtains Diene amide；Molecular formula is as follows：
The wave spectrum of compound two/spectral detection result is as follows：
It is infrared：Peak value is Vmax=3293 (N-H), 2927,2851,1630 (C=O), 1549,1236,999,724, 694cm-1；
Mass spectrum：m/z：384.2897([M+H]+)；
Fig. 3 is the hydrogen nuclear magnetic resonance spectrogram of compound two in the synthetic product of the embodiment of the present invention 1；
Fig. 4 is the carbon-13 nmr spectra figure of compound two in the synthetic product of the embodiment of the present invention 1.
Thus, it is possible to there is N- benzyl -9- carbonyls -10 (E), 12 (Z)-ten eight carbon in confirming the product that embodiment 1 obtains Diene amide；Molecular formula is as follows：
The wave spectrum of compound three/spectral detection result is as follows：
It is infrared：Peak value is Vmax=3311 (N-H), 3294,2917,2848,1681,1640 (C=O), 1551,997, 720,694cm–1；
Mass spectrum：m/z：384.19([M+H]+)；
Fig. 5 is the hydrogen nuclear magnetic resonance spectrogram of compound three in the synthetic product of the embodiment of the present invention 1；Fig. 6 is implemented for the present invention The carbon-13 nmr spectra figure of compound three in the synthetic product of example 1.
Thus, it is possible to there is N- benzyl -13- carbonyls -9 (Z), 11 (E)-ten eight carbon in confirming the product that embodiment 1 obtains Diene amide；Molecular formula is as follows：
To be analyzed more than, the compound that embodiment one is prepared includes N- benzyl -9- carbonyls -10 (E), and 12 (E)-ten eight carbon diene amide；N- benzyl -9- carbonyls -10 (E), 12 (Z)-ten eight carbon diene amide, N- benzyl -13- carbonyls -9 (Z), 11 (E)-ten eight carbon diene amide.
Maca has the formation for significantly increasing sexual desire, regulation bone absorption and new bone.
Three compounds that embodiment one is prepared are prepared as medicine；Said medicine is carried out to mouse respectively to Medicine.With blank control group Comparatively speaking, feeding has the male mice number of copulations of said medicine and female mice pregnancy rate obvious Rise.Illustrate that pharmaceutical composition prepared by three compounds provided in an embodiment of the present invention has antifatigue and improves sexual function Effect.
The preferred embodiments of the present invention are the foregoing is only, are not intended to limit the invention, for the skill of this area For art personnel, the present invention can have various modifications and variations.Within the spirit and principles of the invention, that is made any repaiies Change, equivalent substitution, improvement etc., should be included in the scope of the protection.

Claims (10)

  1. A kind of 1. macamide synthetic method, it is characterised in that including：Linoleic acid is catalyzed oxygen with oxidant by pyridine derivate Change obtains maca ene mixture；Chromatogram is prepared by being used after the maca ene mixture and benzylamine or benzyl amine derivative amidation process Separation；
    Wherein：The oxidant is 2, in 2,6,6- tetramethyl piperidines-nitrogen-oxide, pyridinium tribromide, 2- iodosobenzoic acids It is any；The benzyl amine derivative is 3- methoxybenzyls ammonia or 3,4- dimethoxy benzyl ammonia.
  2. 2. macamide synthetic method according to claim 1, it is characterised in that the linoleic acid and the oxidant are anti- The reaction dissolvent answered is any of DMF, acetonitrile, dichloromethane and dimethyl sulfoxide (DMSO).
  3. 3. macamide synthetic method according to claim 1, it is characterised in that the pyridine derivate is 4- diformazan ammonia Any of yl pyridines, 4- pyrollidinopyridines and 2,6- lutidines.
  4. 4. macamide synthetic method according to claim 1, it is characterised in that the linoleic acid leads to the oxidant The pyridine derivate catalytic oxidation is crossed, including：The pyridine derivate is added in dissolved with the linoleic solvent After reaction, solvent is removed, dissolves residue with dichloromethane, with unsaturated carbonate sodium salt, water washing, dichloromethane is removed, obtains The maca ene mixture.
  5. 5. macamide synthetic method according to claim 1, it is characterised in that the maca ene mixture and the benzyl The reaction reagent of amine amideization reaction is N, N'- carbodicyclo hexylimides, N, N'- DICs, 1- ethyls-(3- Dimethylaminopropyl) phosphinylidyne diimmonium salt hydrochlorate, 2- (7- aoxidize BTA)-N, N, N ', N '-tetramethylurea hexafluoro phosphorus Any of acid esters, hexafluorophosphoric acid BTA -1- bases-epoxide tripyrrole alkyl phosphorus, N, ' N- carbonyl dimidazoles.
  6. 6. macamide synthetic method according to claim 1, it is characterised in that the maca ene mixture and the benzyl The solvent of amine amideization reaction is selected from any of DMF, dichloromethane and dimethyl sulfoxide (DMSO).
  7. 7. macamide synthetic method according to claim 1, it is characterised in that the maca ene mixture and the benzyl After amine amideization reaction, in addition to：Product after the amidation process described in saturated sodium carbonate aqueous salt solu-tion, concentration are gone Except the reaction dissolvent of the amidation process.
  8. 8. macamide synthetic method according to claim 1, it is characterised in that the preparation chromatrographic separation step In, mobile phase is that volume ratio is 70-75:25 organic solvent and water；The organic solvent is 0.01-0.02%vol trifluoro Acetic acidacetonitrile solution, 0.01-0.02%vol acetate-methanol solution, 0.01-0.02%vol formic acid-propanol solution in It is any；The product that absorbing wavelength is 280nm is taken in chromatographic step with preparing described.
  9. 9. a kind of macamide compound, it is characterised in that the macamide compound is as described in claim any one of 1-7 Macamide synthetic method synthesis；
    The macamide compound is：N- benzyl -13- carbonyls -9 (Z), 11 (E)-ten eight carbon diene amide；N- benzyl -9- carbonyls Base -10 (E), 12 (Z)-ten eight carbon diene amide；N- benzyl -9- carbonyls -10 (E), in 12 (E)-ten eight carbon diene amide extremely Few one kind.
  10. 10. the macamide compound described in claim 9 is in preparing antifatigue, anti-senile dementia and improving sexual function medicine Application.
CN201710609418.6A 2017-07-25 2017-07-25 A kind of macamide compound and its synthetic method, application Pending CN107353219A (en)

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CN111153827B (en) * 2020-01-17 2023-05-16 广东药科大学 Preparation method and application of benzylamine omega-3 unsaturated fatty acid

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Application publication date: 20171117