CN110483536A - A kind of tricyclic isoquinoline alkaloid compound extracted from cassia siamea and its application - Google Patents
A kind of tricyclic isoquinoline alkaloid compound extracted from cassia siamea and its application Download PDFInfo
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- CN110483536A CN110483536A CN201910825539.3A CN201910825539A CN110483536A CN 110483536 A CN110483536 A CN 110483536A CN 201910825539 A CN201910825539 A CN 201910825539A CN 110483536 A CN110483536 A CN 110483536A
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- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24D—CIGARS; CIGARETTES; TOBACCO SMOKE FILTERS; MOUTHPIECES FOR CIGARS OR CIGARETTES; MANUFACTURE OF TOBACCO SMOKE FILTERS OR MOUTHPIECES
- A24D3/00—Tobacco smoke filters, e.g. filter-tips, filtering inserts; Filters specially adapted for simulated smoking devices; Mouthpieces for cigars or cigarettes
- A24D3/02—Manufacture of tobacco smoke filters
- A24D3/0204—Preliminary operations before the filter rod forming process, e.g. crimping, blooming
- A24D3/0212—Applying additives to filter materials
- A24D3/022—Applying additives to filter materials with liquid additives, e.g. application of plasticisers
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
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Abstract
The invention discloses a kind of tricyclic isoquinoline alkaloid compound extracted from cassia siamea and its applications.The compound is obtained using cassia siamea branch, leaf as raw material through ethyl acetate extraction, silica gel column chromatography and high performance liquid chromatography separation after purification.Molecular formula is C17H17NO3, there is following structural formula:Compound nomenclature are as follows: 3- hydroxyl -1- (2,2- dimethyl -2H- pyrans [2,3-g] isoquinolin -6- base) pyrans -1- ketone.The compound has the functional group of heavy metal chelating function, can generate stable chelate with heavy metal element；Addition is using having the effect of significant decrease cigarette flue gas heavy metal element in cigarette filter, while not negatively affecting significantly to cigarette smoke and the original sense of taste harmony of cigarette is good, also has slight improvement result to the irritation of cigarette smoking and pleasant impression.Raw materials for production distribution of the present invention is wide, and biological yield is big, and compound preparation process is simple, and production cost is low, industrial application easy to accomplish.
Description
Technical field
The invention belongs to technical field of phytochemistry, be specifically related to a kind of branch from leguminosae cassia plant cassia siamea,
Isolated tricyclic isoquinoline alkaloid compound is extracted in leaf for the first time.The compound has the official of heavy metal chelating function
Energy group can generate stable chelate with free state heavy metal element, and therefore, the invention further relates to the compounds to reduce volume
Application in cigarette flue gas heavy metal content.
Background technique
Cassia siamea (scientific name: Cassia siamea Lam.), gains the name due to material is hard, knife axe difficulty enters.Leguminosae cassia
Aiphyllium, it is about 10 meters high；Bark grey, dipped beam is sliding, slightly lobe；Spray has cord, dredges by pubescence.Leaf is 20-30 lis long
Rice；Rachis and petiole Non-gland body, by micro- pubescence；Leaflet is to life.Raceme is born in the axil of shoot apex, is arranged into umbrella room flower
Sequence shape；Bract is linear；Sepal subcircular；Petal yellow, wealthy obovate.Pod is flat, and edge thickeies；10-20, seed.Florescence
The 10-11 month；Fruiting period December-January in next year.This kind is with a long history in Chinese cultivated, Fujian, Taiwan, Guangdong, Hainan, Guangxi, Yunnan
There is extensive plantation in south and western part, wherein the firewood forests cultivation history with Jinghong In Yunnan Province is longer.Due to timber hard and compact,
Resistance to water-wet is first-class furniture raw material not by worm oyster.Veteran material black, texture is very beautiful, can decorate for musical instrument.Rapidly because of its growth,
Rudiment power is strong, and limb is inflammable, and firepower is prosperous, largely cultivates in Yunnan and makees firewood forests, is cut down using head operation, two Nian Shugao after cutting
Up to 3-4 meters, it can generally take turns within every 4 years and cut down once.Domestic and foreign scholars carried out some researchs to cassia siamea, the chemical combination mainly reported
Species type has: chromogen ketone, flavonoids, Anthraquinones, terpene, steroid, alkaloids etc..
The heavy metal elements such as As, Pb, Cd, Ni, Cr are the harmful substance in Hoffman list in cigarette mainstream flue gas.Have
Studies have shown that tobacco-using male blood cadmium concentration is obviously higher than non-smoker.Therefore, cigarette micro heavy control is to be related to smoking
The major issue of safety, how research, which reduces the content of beary metal during cigarette is burnt and sucked, has important scientific meaning and answers
With value.
The present invention has extracted a kind of new tricyclic isoquinoline biology isolated by the research to cassia siamea chemical component
Relevant report is not yet seen in alkaloid compound, the compound.It is worth mentioning that the compound has heavy metal element chela
The group of function is closed, stable five-membered ring chelate can be generated with heavy metal element, and can effectively retain cigarette mainstream flue gas
In heavy metal element, have the function of significantly reduce cigarette flue gas heavy metal element content.
Summary of the invention
The purpose of the present invention is to provide a kind of new tricyclic isoquinoline alkaloid compounds.
It is a further object to provide a kind of methods for preparing the tricyclic isoquinoline alkaloid compound.
The object of the invention is also to provide the tricyclic isoquinoline alkaloid compounds to reduce cigarette mainstream flue gas
Application in contents of heavy metal elements.
The purpose of the present invention is achieved by the following technical programs.
Unless otherwise indicated, percentage employed in the present invention is mass percent.
A kind of tricyclic isoquinoline alkaloid compound, molecular formula C17H17NO3, there is following structural formula:
The Compound nomenclature are as follows: 3- hydroxyl -1- (2,2- dimethyl -2H- pyrans [2,3-g] isoquinolin -6- base) pyrans -1-
Ketone, English name are as follows: 3-hydroxy-1- (2,2-dimethyl-2H-pyrano [2,3-g] isoquinolin-6-yl)
propan-1-one。
The method for preparing the tricyclic isoquinoline alkaloid compound, comprising the following steps:
(1) medicinal extract extracts: taking cassia siamea branch, leaf to dry, is crushed to 35~60 mesh, it is anti-that smashed sample is placed in glass
It answers in kettle, is extracted 2 times with 95% alcohol reflux, merge extracting solution twice and be concentrated to small size, it is then molten with 3% tartaric acid
Liquid dilution, then be extracted with ethyl acetate 2 times；Water phase is saturated with sodium carbonate after having extracted, and is extracted with ethyl acetate again 2 times, is closed
And the ethyl acetate phase extracted, alkaloid position medicinal extract is concentrated under reduced pressure to obtain；
(2) silica gel column chromatography: the acetone or methanol that medicinal extract obtained by step (1) is measured with 1.5~3 times of weight ratio dissolve, so
0.8~1.6 times of medicinal extract weight of 80~100 mesh silica gel mixed samples are used afterwards；Dress column silica gel is 160~200 mesh, and dosage is medicinal extract weight
3~8 times；Gradient elution is carried out with the chloroform of volume ratio 20:1,9:1,8:2,7:3,6:4 and 1:1-acetone mixed solvent, is received
Collect gradient eluent, concentration, is monitored through TLC, merge identical part；
(3) high performance liquid chromatography separation: chloroform-acetone eluant of 8:2 is taken to carry out high performance liquid chromatography separation purifying: with
62% methanol aqueous solution is mobile phase, and 21.2 × 250mm, 5 μm of ZorbaxPrepHT GF reverse phase preparative column is stationary phase, stream
Fast 20mL/min, UV detector Detection wavelength are 346nm, and each 0.5~1.0mL of sample introduction collects the chromatographic peak of 32.9min,
It is evaporated after repeatedly adding up to get the tricyclic isoquinoline alkaloid compound crude product.
In step (3), the crude compound obtained after high pressure liquid chromatography isolates and purifies is dissolved with pure methanol again, and with
Pure methanol is mobile phase, with sephadex column chromatography for separation, obtained yellow jelly, as pure compounds.
The Structural Identification of compound:
The compounds of this invention is yellow jelly, and HRESI-MS shows that its quasi-molecular ion peak is 306.1112 [M+Na]+,
In conjunction with1H and13C H NMR spectroscopy determines that molecular formula is C17H17NO3, it is alkaloid compound, and the degree of unsaturation of compound is 10.
Its infrared spectroscopy, which is shown in compound, hydroxyl (3386cm-1), carbonyl (1665cm-1) and aromatic ring (1612,1568 and 1440cm-1) signal, ultraviolet spectra has absorption maximum to also confirm that there are aromatic ring structures in compound in 225,273,310 and 346nm.Chemical combination
Object1H、13C-NMR and DEPT spectrum (table -1) shows that it contains 17 carbon and 17 hydrogen.It include: the isoquinoline that a 1,6,7- replaces
Quinoline parent nucleus (C-1~C-10；H-3, H-4, H-5 and H-8), a humorous dimethyl chromene ring (- CH=CH-C (CH3)2- O-, C-1 "
~C-5 ", H-1 ", H-2 " and H6- 4 ", 5 "), a 3- hydroxyl propyl- 1- ketone group (- CO-CH2CH2-OH；C-1 '~C-3 '；H2-2′
And H2-3′).The presence of isoquinolin parent nucleus can pass through H-3 in compound and C-1, C-4, C-10；H-4 and C-3, C-5, C-9, C-
10；H-5 and C-4, C-9, C-10；And H-8 (figure -3) related to the HMBC of C-1, C-9, C-10 is confirmed；Humorous dimethyl chromene ring
Presence can pass through H-1 " and C-2 ", C-3 ", H-2 " and C-1 ", C-3 ", C-4 ", 5 " and H6- 4 ", 5 " and C-2 ", C-3 "
HMBC correlation is confirmed；The presence of 3- hydroxyl propyl- 1- ketone group can pass through H2- 2 ' and H2- 3 '1H-1H COSY is related, and
H2- 2 ' and C-1 ', C-3 ', H3- 3 ' related to the HMBC of C-1 ', C-2 ' be confirmed.Further analyze its HMBC Correlated Spectroscopy, root
According to H-1 " and C-5, C-6, C-7；H-2 " and C-7 and H-8 is related to the HMBC of C-1 ", can speculate that gem-dimethyl chromene ring takes
In generation, is at C-6 and C-7 of isoquinolin phenyl ring, and the position C-1 " carbon is connected to the position C-7 of isoquinolin phenyl ring.So far, compound
Precursor structure can be identified as the iloquinoline derivative tricyclic alkaloid with gem-dimethyl chromene ring.It is remaining after the parent nucleus of compound determines
3- hydroxyl propyl- 1- ketone group can be set to substituent group.Pass through H2- 2 ' related to the HMBC of C-1, it may be determined that 3- hydroxyl propyl- 1- ketone group
It is substituted in C-1.So far the structure of the compounds of this invention is confirmed, the Compound nomenclature are as follows: 3- hydroxyl -1- (2,2- dimethyl -
2H- pyrans [2,3-g] isoquinolin -6- base) pyrans -1- ketone (1).
Table -1, compound1H and13C nuclear magnetic resonance data (solvent C DCl3, 500 and 125MHz)
Infrared, the ultraviolet and mass spectrometric data of compound: UV (methanol), λmax(logε)225(4.26)、273(3.68)、310
(3.43),346(3.62)；IR (pressing potassium bromide troche): νmax 3386、3065、2948、1665、1612、1568、1440、1352、
1244、1163、1057、857、760cm-1；1H and13C NMR data (500 and 125MHz, (CDCl3), it is shown in Table -1；Cation mould
Formula ESIMS m/z 306 [M+Na]+；Positive ion mode HRESIMS m/z 306.1112 [M+Na]+(calculated value C17H17NNaO3,
306.1106)。
Tricyclic isoquinoline alkaloid compound of the invention is in reducing cigarette mainstream flue gas contents of heavy metal elements
Using.
1, the heavy metal complex Measurement of Stability Constants of compound:
Since the nitrogen of isoquinolin in the compounds of this invention and ketonic oxygen can be coordinated with heavy metal atom, stable five yuan are formed
Ring chelate.Therefore the chelate stability constant for the classical way measurement the compounds of this invention for using Scogs and Miniquad to develop.
The result shows that: the compounds of this invention and the high heavy metal element of four kinds of arsenic, lead, cadmium, mercury toxicity (pH 6.2 in neutral medium
~7.9) stable chelate, stability constant (lg can be generatedKMY) it is respectively as follows: 19.6,23.4,25.8 and 20.2.
2, adding method and flue gas heavy metal element reducing effect analysis of the compound in cigarette filter:
The tricyclic isoquinoline alkaloid compound is made into the solution of 0.5mg/mL with triacetyl glycerine.It is rolling up
It in cigarette filter tip forming process, is equably sprayed on filter tow by the 5-8% of filter tow weight, filter stick is made, then will
The filter stick and cigarette cigarette are fabricated to cigarette, for cigarette flue gas heavy metal element determination.
Main flume analysis, flue gas heavy metal element determination are carried out to the cigarette for being added to the compounds of this invention in filter stick
It is carried out referring to China's tobacco industry standard (YC/T 389-2011 and YCT 404-2011), and to be not added with the compounds of this invention
Cigarette of the same race as control, by with control sample compare calculate heavy metal element reduced rate.
The result shows that: 6 kinds of different size cigarette flue gas heavy metal burst sizes for adding the compounds of this invention are respectively as follows: arsenic
0.367~0.552 μ g/20 branch, 2.48~3.46 μ g/20 branch of lead, 3.15~4.38 μ g/20 branch of cadmium, 0.136~0.205 μ g/ of mercury
20, the control cigarette flue gas heavy metal burst size for being not added with the compounds of this invention is respectively as follows: 0.533~0.792 μ g/20 of arsenic
Branch, 4.82~6.77 μ g/20 branch of lead, 5.70~8.92 μ g/20 branch of cadmium, 0.224~0.375 μ g/20 branch of mercury, four heavy metal species member
The reduced rate of element is respectively as follows: arsenic 26.2%~34.1%, lead 44.8%~47.2%, cadmium 44.0%~49.1%, mercury 32.4%
~43.5%；Have the effect of significantly reducing contents of heavy metal elements in cigarette mainstream flue gas.
3, toxicological evaluation and sensory evaluating smoking:
Toxicological analysis has been carried out to the cigarette smoke condensate for being added to the compounds of this invention in filter stick.Cytotoxicity is real
It tests, three Salmonella reversion test, micronucleus test in vitro in vitro toxicology test results show: using the one-way of SPSS software
The cell inhibitory rate that ANOVA generates given the test agent and control sample cigarette smoke condensates carries out statistical analysis, three
In item toxicological experiment, no difference of science of statistics (P between the cigarette of the compounds of this invention and the smoke's total particulate matter of control cigarette is added
>0.05)。
Sensory evaluation also is carried out to the cigarette for being added to the compounds of this invention, and to be not added with the identical cigarette of the compound
As control.Evaluation and analysis the result shows that: add the cigarette and control sensory evaluating smoking's result difference very little of the compounds of this invention, it is main poor
Not Wei entrance slightly return sweet tea sense and the original sense of taste harmony of cigarette is good, do not negatively affect significantly；And to cigarette smoking
Irritation and pleasant impression have slight improvement result.
Compared with prior art, the invention has the following advantages that
(1) present invention extracts a kind of isolated tricyclic isoquinoline alkaloid for the first time from leguminosae cassia plant cassia siamea
Class compound, the compound have the functional group of heavy metal chelating function, can generate stable chelate with heavy metal element；
Addition, which uses, in cigarette filter has the effect of significantly reducing cigarette flue gas heavy metal element, while not bright to cigarette smoke
The original sense of taste harmony of aobvious negative effect and cigarette is good, also has slight improve to make the irritation of cigarette smoking and pleasant impression
With.
(2) cassia siamea feed distribution is wide, largely cultivates in Yunnan and makees firewood forests, is cut down using head operation, 2 years after cutting
Up to 3-4 meter of tree, it can generally take turns within every 4 years and cut down once, biological yield is very big, and raw material is easy to get, is at low cost, industry easy to accomplish
Change application.
(3) the compounds of this invention is safe and nontoxic, preparation process is simple, has the condition of large-scale promotion application.
Detailed description of the invention
Fig. 1 be tricyclic isoquinoline alkaloid compound of the present invention carbon-13 nmr spectra (13C NMR)；
Fig. 2 be tricyclic isoquinoline alkaloid compound of the present invention nuclear magnetic resonance spectroscopy (1H NMR)；
Fig. 3 be tricyclic isoquinoline alkaloid compound of the present invention crucial HMBC with1H-1HCOSY correlation figure.
Specific embodiment
The present invention is described in further detail with reference to the accompanying drawings and examples, but drawings and examples are not pair
The restriction of technical solution of the present invention, it is all based on present invention teach that made variation or equivalent replacement, should belong to the present invention
Protection scope.
Cassia siamea as described in the examples is not limited by area and kind, and the present invention may be implemented.
Embodiment 1
Cassia siamea sample is derived from In Xishuangbanna of Yunnan.Dry cassia siamea branch, leaf 5.2kg are taken, about 35~60 mesh are crushed to,
It is placed in the glass reaction kettle of 20L, 95% 6~10L of ethyl alcohol is added, 35~60min of refluxing extraction filters out extracting solution；Again
95% 6~10L of ethyl alcohol, 35~60min of refluxing extraction are added into filter residue, filters out extracting solution, merges extracting solution twice and is concentrated
To small size.Then it is diluted with 3% 4~6L of tartaric acid solution, is extracted 2 times with the ethyl acetate of 4~6L.Water phase after having extracted
It is saturated with sodium carbonate, is extracted 2 times with the ethyl acetate of 4~6L again, merge the ethyl acetate phase of extraction, be concentrated under reduced pressure biological
Alkali position medicinal extract 33.5g.The acetone solution of 60g is added in medicinal extract, 100 mesh silica gel 45g are then added and mix sample, after mixing sample, uses
200 mesh silica gel 120g fill column；Chloroform-acetone the mixing for being respectively 20:1,9:1,8:2,7:3,6:4 and 1:1 with volume ratio is organic
Solvent gradient elution collects gradient eluent, concentration, monitors through TLC, merge identical part, obtain 6 part A-F,
In, to the sample C (8:2) being collected into again with 21.2 × 250mm, 5 μm of Zorbax PrepHT GF reverse phase preparative column is to fix
Phase, 62% methanol are mobile phase, and flow velocity 20mL/min, UV detector Detection wavelength is 346nm, each sample introduction 0.8mL, is received
Collect the chromatographic peak of 32.9min, is evaporated after repeatedly adding up to get the tricyclic isoquinoline alkaloid compound crude product.Compound
Crude product is dissolved with pure methanol again, and using pure methanol as mobile phase, with sephadex column chromatography for separation, collects alkaloid of the present invention
Class compound flows out part, and the yellow jelly that solvent evaporated obtains, solvent evaporated is pure compounds.
Embodiment 2
Cassia siamea is taken at Yuanjiang County of Yunnan.Sample comminution weighs the smashed sample of 7.2kg, is placed in the glass of 20L to 45 mesh
In reaction kettle, 95% ethyl alcohol 10L is added, refluxing extraction 50min filters out extracting solution；95% second is added into filter residue again
Alcohol 10L, refluxing extraction 50min filter out extracting solution, merge extracting solution twice and are concentrated to small size.Then molten with 3% tartaric acid
Liquid 8L dilution is extracted 2 times with the ethyl acetate of 8L.Water phase is saturated with sodium carbonate after having extracted, and is extracted again with the ethyl acetate of 8L
It takes 2 times, merges the ethyl acetate phase of extraction, alkaloid position medicinal extract 45.6g is concentrated under reduced pressure to obtain.The third of 80g is added in medicinal extract
Ketone dissolution, is then added 100 mesh silica gel 60g and mixes sample, after mixing sample, fills column with 180 mesh silica gel 200g；It is respectively 20 with volume ratio:
The chloroform of 1,9:1,8:2,7:3,6:4 and 1:1-acetone mixed organic solvents gradient elution collect gradient eluent, concentration, warp
TLC monitoring, merges identical part, obtains 6 part A-F, wherein to the part sample C (8:2) being collected into again with 21.2 ×
250mm, 5 μm of Zorbax PrepHT GF reverse phase preparative column are stationary phase, and 62% methanol is mobile phase, flow velocity 20mL/
Min, UV detector Detection wavelength are 346nm, and each sample introduction 1.0mL collects the chromatographic peak of 32.9min, are steamed after repeatedly adding up
It does to get the tricyclic isoquinoline alkaloid compound crude product.Crude compound is dissolved with pure methanol again, and is with pure methanol
Mobile phase is collected alkaloid compound of the present invention and flows out part, solvent evaporated is to change with sephadex column chromatography for separation
Close object sterling.
Embodiment 3
The structure for the tricyclic isoquinoline alkaloid compound that embodiment 1 is prepared is identified by the following method:
Compound is yellow jelly, and HRESI-MS shows that its quasi-molecular ion peak is 306.1112 [M+Na]+, in conjunction with1H
With13C H NMR spectroscopy determines that molecular formula is C17H17NO3, it is alkaloid compound, and the degree of unsaturation of compound is 10.Its is infrared
Spectrum, which is shown in compound, hydroxyl (3386cm-1), carbonyl (1665cm-1) and aromatic ring (1612,1568 and 1440cm-1) signal,
Ultraviolet spectra has absorption maximum to also confirm that there are aromatic ring structures in compound in 225,273,310 and 346nm.Compound1H、13C-NMR and DEPT spectrum (table -1) shows that it contains 17 carbon and 17 hydrogen.It include: the isoquinolin parent nucleus that a 1,6,7- replaces
(C-1~C-10；H-3, H-4, H-5 and H-8), a humorous dimethyl chromene ring (- CH=CH-C (CH3)2- O-, C-1 "~C-
5 ", H-1 ", H-2 " and H6- 4 ", 5 "), a 3- hydroxyl propyl- 1- ketone group (- CO-CH2CH2-OH；C-1 '~C-3 '；H2- 2 ' and H2-
3′).The presence of isoquinolin parent nucleus can pass through H-3 in compound and C-1, C-4, C-10；H-4 and C-3, C-5, C-9, C-10；H-5
With C-4, C-9, C-10；And H-8 (figure -3) related to the HMBC of C-1, C-9, C-10 is confirmed；The presence of humorous dimethyl chromene ring
H-1 " and C-2 ", C-3 ", H-2 " and C-1 ", C-3 ", C-4 ", 5 " and H can be passed through6- 4 ", the HMBC phase of 5 " and C-2 ", C-3 "
Pass is confirmed；The presence of 3- hydroxyl propyl- 1- ketone group can pass through H2- 2 ' and H2- 3 '1H-1H COSY correlation and H2- 2 ' with
C-1 ', C-3 ', H3- 3 ' related to the HMBC of C-1 ', C-2 ' be confirmed.Its HMBC Correlated Spectroscopy is further analyzed, according to H-1 "
With C-5, C-6, C-7；H-2 " and C-7 and H-8 is related to the HMBC of C-1 ", and it is different can to speculate that gem-dimethyl chromene ring is substituted in
C-6 and C-7 of quinoline phenyl ring, and the position C-1 " carbon is connected to the position C-7 of isoquinolin phenyl ring.So far, the parent knot of compound
Structure can be identified as the iloquinoline derivative tricyclic alkaloid with gem-dimethyl chromene ring.After the parent nucleus of compound determines, remaining 3- hydroxyl
Base propyl- 1- ketone group can be set to substituent group.Pass through H2- 2 ' related to the HMBC of C-1, it may be determined that 3- hydroxyl propyl- 1- ketone group is substituted in
C-1.So far the structure of the compounds of this invention is confirmed, the Compound nomenclature are as follows: 3- hydroxyl -1- (2,2- dimethyl -2H- pyrroles
Mutter [2,3-g] isoquinolin -6- base) pyrans -1- ketone.
Embodiment 4
Compound prepared by Example 2 is yellow jelly.Measurement is identical as implementing 3, prepared by confirmation embodiment 2
Compound is tricyclic isoquinoline alkaloid compound --- 3- hydroxyl -1- (2,2- dimethyl -2H- pyrans [2,3-g] isoquinoline
Quinoline -6- base) pyrans -1- ketone.
Embodiment 5
Since the nitrogen of isoquinolin in the compounds of this invention and ketonic oxygen can be coordinated with heavy metal atom, stable five yuan are formed
Ring chelate.The chelate of the compounds of this invention is determined in the present invention using the classical way that Scogs and Miniquad is developed
Stability constant.The result shows that: the compounds of this invention and the high heavy metal element of four kinds of arsenic, lead, cadmium, mercury toxicity are in neutral medium
(pH is 6.2~7.9) can generate stable chelate, stability constant (lgKMY) it is respectively as follows: 19.6,23.4,25.8 and
20.2。
Embodiment 6
The tricyclic isoquinoline alkaloid compound is made into the solution of 0.5mg/mL with triacetyl glycerine.It is rolling up
It in cigarette filter tip forming process, is uniformly sprayed on filter tow by the 5-8% of filter tow weight, filter stick is made, then will
The filter stick and cigarette cigarette are fabricated to cigarette, for cigarette flue gas heavy metal element determination.
Main flume analysis, flue gas heavy metal element determination are carried out to the cigarette for being added to the compounds of this invention in filter stick
It is carried out referring to China's tobacco industry standard (YC/T 389-2011 and YCT 404-2011), and to be not added with the compounds of this invention
Cigarette as control, by with control sample compare calculate heavy metal element reduced rate.
The result shows that: 6 kinds of different size cigarette flue gas heavy metal burst sizes for adding the compounds of this invention are respectively as follows: arsenic
0.367~0.552 μ g/20 branch, 2.48~3.46 μ g/20 branch of lead, 3.15~4.38 μ g/20 branch of cadmium, 0.136~0.205 μ g/ of mercury
20, the control cigarette flue gas heavy metal burst size for being not added with the compounds of this invention is respectively as follows: 0.533~0.792 μ g/20 of arsenic
Branch, 4.82~6.77 μ g/20 branch of lead, 5.70~8.92 μ g/20 branch of cadmium, 0.224~0.375 μ g/20 branch of mercury, four heavy metal species member
The reduced rate of element is respectively as follows: arsenic 26.2%~34.1%, lead 44.8%~47.2%, cadmium 44.0%~49.1%, mercury 32.4%
~43.5%；Have the effect of significantly reducing contents of heavy metal elements in cigarette mainstream flue gas.
Embodiment 7
Toxicological analysis has been carried out to the cigarette smoke condensate for being added to the compounds of this invention in filter stick.Cytotoxicity is real
It tests, three Salmonella reversion test, micronucleus test in vitro in vitro toxicology test results show: using the one-way of SPSS software
The cell inhibitory rate that ANOVA generates given the test agent and control sample cigarette smoke condensates carries out statistical analysis, three
In item toxicological experiment, no difference of science of statistics (P between the cigarette of the compounds of this invention and the smoke's total particulate matter of control cigarette is added
>0.05)。
Sensory evaluation is carried out to the cigarette for being added to the compounds of this invention, and to be not added with the identical cigarette of compound work
For control.Evaluation and analysis the result shows that: add the compounds of this invention cigarette and control sensory evaluating smoking's result difference very little, essential difference
Sweet tea sense is slightly returned for entrance and the original sense of taste harmony of cigarette is good, is not negatively affected significantly；And to cigarette smoking
Irritation and pleasant impression have slight improvement result.
Claims (5)
1. a kind of tricyclic isoquinoline alkaloid compound, molecular formula C17H17NO3, there is following structural formula:
The Compound nomenclature are as follows: 3- hydroxyl -1- (2,2- dimethyl -2H- pyrans [2,3-g] isoquinolin -6- base) pyrans -1- ketone,
English name are as follows: 3-hydroxy-1- (2,2-dimethyl-2H-pyrano [2,3-g] isoquinolin-6-yl) propan-1-
one。
2. the preparation method of tricyclic isoquinoline alkaloid compound described in claim 1, comprising the following steps:
(1) medicinal extract extracts: taking cassia siamea branch, leaf to dry, is crushed to 35~60 mesh, smashed sample is placed in glass reaction kettle
In, it is extracted 2 times with 95% alcohol reflux, merges extracting solution twice and be concentrated to small size, it is then dilute with 3% tartaric acid solution
It releases, then is extracted with ethyl acetate 2 times；Water phase is saturated with sodium carbonate after having extracted, and is extracted with ethyl acetate again 2 times, and extraction is merged
Alkaloid position medicinal extract is concentrated under reduced pressure to obtain in the ethyl acetate phase taken；
(2) silica gel column chromatography: the acetone or methanol that medicinal extract obtained by step (1) is measured with 1.5~3 times of weight ratio dissolve, and then use
0.8~1.6 times of medicinal extract weight of 80~100 mesh silica gel mixed samples；Dress column silica gel is 160~200 mesh, and dosage is the 3 of medicinal extract weight
~8 times；Gradient elution is carried out with the chloroform of volume ratio 20:1,9:1,8:2,7:3,6:4 and 1:1-acetone mixed solvent, collects ladder
Eluent, concentration are spent, is monitored through TLC, merges identical part；
(3) high performance liquid chromatography separation: chloroform-acetone eluant of 8:2 is taken to carry out high performance liquid chromatography separation purifying: with 62%
Methanol aqueous solution is mobile phase, and 21.2 × 250mm, 5 μm of Zorbax PrepHT GF reverse phase preparative column is stationary phase, flow velocity
20mL/min, UV detector Detection wavelength are 346nm, and each 0.5~1.0mL of sample introduction collects the chromatographic peak of 32.9min, more
It is secondary it is cumulative after be evaporated to get the tricyclic isoquinoline alkaloid compound crude product.
3. preparation method according to claim 2, it is characterised in that: in step (3), isolated and purified through high pressure liquid chromatography
The crude compound obtained afterwards is dissolved with pure methanol again, and using pure methanol as mobile phase, with sephadex column chromatography for separation, is obtained
The yellow jelly arrived, as pure compounds.
4. tricyclic isoquinoline alkaloid compound described in claim 1 is reducing cigarette mainstream flue gas contents of heavy metal elements
In application.
5. application according to claim 4, it is characterised in that: with triacetyl glycerine that the tricyclic isoquinoline is biological
Alkaloid compound is made into the solution of 0.5mg/mL, and is equably sprayed on filter tow by the 5-8% of filter tow weight, it
Routinely cigarette filter tip rod is rolled up in technique production afterwards.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5162335A (en) * | 1986-05-21 | 1992-11-10 | Duphar International Research B.V. | Di- and tetrahydroisoquinoline derivatives |
| CN106117138A (en) * | 2016-06-29 | 2016-11-16 | 云南中烟工业有限责任公司 | A kind of isoquinoline alkaloids alkaloid compound, its preparation method and application with antibacterial activity |
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2019
- 2019-09-03 CN CN201910825539.3A patent/CN110483536B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5162335A (en) * | 1986-05-21 | 1992-11-10 | Duphar International Research B.V. | Di- and tetrahydroisoquinoline derivatives |
| CN106117138A (en) * | 2016-06-29 | 2016-11-16 | 云南中烟工业有限责任公司 | A kind of isoquinoline alkaloids alkaloid compound, its preparation method and application with antibacterial activity |
Non-Patent Citations (1)
| Title |
|---|
| 高璇，等: "卷烟微量重金属控制技术研究", 《山东农业大学学报（自然科学版）》 * |
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