CN103554125B - 4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen is for podophyllotoxin derivative and Synthesis and applications - Google Patents

4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen is for podophyllotoxin derivative and Synthesis and applications Download PDF

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CN103554125B
CN103554125B CN201310521288.2A CN201310521288A CN103554125B CN 103554125 B CN103554125 B CN 103554125B CN 201310521288 A CN201310521288 A CN 201310521288A CN 103554125 B CN103554125 B CN 103554125B
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podophyllotoxin
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徐晖
樊玲玲
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Northwest A&F University
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Abstract

The present invention discloses a series of 4 alpha-acyloxies-2 ' (2 ', 6 '), 2 ��-many halogen for podophyllotoxin derivative and preparation method, these serial 4 alpha-acyloxies-2 ' (2 ', 6 '), 2 ��-many halogen for the chemical general formula of podophyllotoxin derivative is:In formula, X=Cl, Y=H; Or, X=Y=Cl; Or, X=Br, Y=H. Its preparation method is, taking podophyllotoxin as raw material goes protection obtained 2 ' (2 ', 6 ') by E-ring halogen generation, C-4 position hydroxyl protection, C-2 position alpha-chloro, C-4 position, 2 ��-many halogen for podophyllotoxin, finally with DMAP/DCC or BF3��Et2O obtained for 4-2 ' (2 ', 6 ') of alpha-acyloxy as esterifying reagent C-4 position-OH and 11 kinds of carboxylic acid reactions, 2 ��-many halogen for podophyllotoxin derivative, with BF3��Et2As being attended by during esterifying reagent, C-ring arylation product generates O. Prove through test, this 4 alpha-acyloxy-2 ' (2 ', 6 '), 2 ��-many halogen has good insecticidal activity for podophyllotoxin derivative, part is higher than podophyllotoxin, wherein the insecticidal activity of some compound is all higher than the botanical pesticide Toosendanin of commercialization, is expected to the plant insecticide for the preparation of high-efficiency low-toxicity.

Description

4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen is for podophyllotoxin derivative and Synthesis and applications
Technical field
The present invention relates to series 4 alpha-acyloxy-2 ' (2 ' with insecticidal activity, 6 '), 2 ��-many halogen is for podophyllotoxin derivative and its preparation method, and these serial 4 alpha-acyloxies-2 ' (2 ', 6 '), 2 ��-many halogen for podophyllotoxin derivative in the application prepared in plant insecticide.
Background technology
Podophyllotoxin is a kind of cyclolignolide with good biological activity, obtains early than separation in the mayapple of America, and the Dysosma versipellis being mainly present in Berberidaceae belongs to, in Diphylleia and Sinopodophyllum. receive much concern because it has isoreactivity antitumor, antiviral, antimycotic. as: the derivative of podophyllotoxin relies on pool two (Etoposide, VP-16) and for Buddhist nun two (Teniposide are moored, VM-26) small cell lung cancer, emerald green ball cancer, acute leukemia, malignant lymphoma etc. all there are is obvious restraining effect, and it has been widely used in clinical, document [CatherineTung-LingLee, VictorChih-KuangLin, Shun-XiangZhang, Xiao-KangZhu, DavidVanVliet, HongHu, ScottA.Beers, Zhe-QingWang, L.MarkCosentino, SusanL.Morris-Natschke, Kuo-HsiungLee.Anti-AIDSagents.291.Anti-HIVactivityofmodi fiedpodophyllotoxinderivatives.Bioorganic&MedicinalChemi stryLetters.1997, 7 (22), 2897-2902] report the activity that 4-nitrogen replacement podophyllotoxin derivative has anti-HIV-1. in recent years, it has been found that multiple agriculture and forestry injurious insect is had by podophyllotoxin analogue refuses food, poisoning and Growth inhibition. as: document [Fu Changbin, Zhang Xing. the impact that bollworm is grown by Sabina vulgaris fruit extract. Northwest Agricultural University journal .1998, 6 (1), 8-12], [Fu Changbin, Zhang Xing. sand ground cypress extract is on the impact of mythimna separata intestinal tissue. Northwest Agricultural University journal .1998, 6 (3), 6-10] and [Zhang Xing, Fu Changbin, the new pesticide plant Sabina vulgaris research progress of the .1995. such as Gao Congfen. Northwest Agricultural University journal .1995, 3 (4), 53-57] report the Deoxypodophyllotoxin contained in Sabina vulgaris there is insecticidal activity, small cabbage moth is had antifeedant activity by it, mythimna separata is refused food and stomach toxicity cytotoxicity, bollworm is had Developing restraint growth effect, to red flour beetle, sitophilus zea-mais has very strong population inhibition, particularly cabbage caterpillar is had very strong antifeedant activity. document [HuiXu, ZhangJunLiang.Naturalproducts-basedinsecticidalagents11. Synthesisandinsecticidalactivityofnovel4 ��-arylsulfonyloxybenzyloxy-2 ��-chloropodophyllotoxinderivativesagainstMythimnaseparataW alkerinvivo.Bioorganic&MedicinalChemistryLetters.2011,21 (18), 5174-5180] and document [HuiXu, XiaoXiao, Qing-tianWang.Naturalproducts-basedinsecticidalagents7.S emisynthesisandinsecticidalactivityofnovel4a-alkyloxy-2-chloropodophyllotoxinderivativesagainstMythimnaseparataW alkerinvivo.Bioorganic&MedicinalChemistryLetters.2010,20 (17), 5009-5012] report 2 ��-chlorine for the synthesis of podophyllotoxin derivative and the research in insecticidal activity. but, the synthesis of 2 alpha-chloro podophyllotoxin ester classes and the research in insecticidal activity in E-ring halogen generation have not been reported.
Summary of the invention
It is an object of the present invention to provide 4-2 ' (2 ', 6 ') of alpha-acyloxy that series is new, 2 ��-many halogen is for podophyllotoxin derivative, and gives preparation method. Experimentally proving, these serial 4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen has higher insecticidal activity for podophyllotoxin derivative, can be used for preparing plant insecticide.
For realizing above-mentioned task, the present invention is achieved by following technical measures:
4-2 ' (2 ', 6 ') of alpha-acyloxy of series, 2 ��-many halogen is for podophyllotoxin derivative, it is characterised in that, these serial 4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen for the chemical general formula of podophyllotoxin derivative is:
In formula, X=Cl, Y=H; Or, X=Y=Cl; Or, X=Br, Y=H.
Above-mentioned 4 alpha-acyloxies-2 ' (2 '; 6 '); 2 ��-many halogen is for the preparation method of podophyllotoxin derivative; it is characterized in that; it is that raw material goes protection obtained 2 ' (2 ' by E-ring halogen generation, C-4 position hydroxyl protection, C-2 position alpha-chloro, C-4 position taking podophyllotoxin; 6 '); 2 ��-many halogen is for podophyllotoxin derivative; 4 alpha-acyloxies-2 ' (2 ' are finally obtained respectively with 11 kinds of carboxylic acid reactions; 6 '); 2 ��-many halogen, for podophyllotoxin derivative, specifically follows these steps to preparation:
By 2 ' (2 ', 6 '), 2 ��-many halogen is dissolved in methylene dichloride for podophyllotoxin, carboxylic acid and DMAP (DMAP), appropriate dewatering agent N is added after at room temperature stirring, N'-dicyclohexylcarbodiimide (DCC), then room temperature reaction it is placed in, TLC tracing detection, reaction is filtered after terminating, remove dicyclohexylurea (DCU) solid, filtrate adds with dichloromethane extraction after a small amount of water, merges with anhydrous sodium sulfate drying after organic phase, concentrated steam dry after be separated by preparation silica gel thin sheet and to obtain required sterling;
Or, by 2 ' (2 ', 6 '), 2 ��-many halogen is dissolved in q. s. methylene chloride for podophyllotoxin and carboxylic acid, after stirring, adds BF under ice salt is bathed3��Et2O, under agitation returns to room temperature, TLC tracing detection, after reaction terminates, adds with dichloromethane extraction after a small amount of water in reaction solution, merges with anhydrous sodium sulfate drying after organic phase, concentrated steam dry after be separated by preparation silica gel thin sheet and to obtain required sterling.
The experiment proved that, 4 alpha-acyloxies-2 ' (2 ' of the present invention, 6 '), agriculture and forestry injurious insect mythimna separata is had by 2 ��-many halogen for podophyllotoxin derivative refuses food cytotoxicity, and the activity of part of compounds is higher than the botanical pesticide Toosendanin now listed, can be used for preparing excellent plant insecticide.
Accompanying drawing explanation
Fig. 1 and Fig. 2 is respectively hydrogen spectrum and the carbon spectrum of compound 5.
The present invention is elaborated further by the embodiment provided below by way of accompanying drawing and contriver.
Embodiment
4 serial new-2 ' (2 ', 6 ') of alpha-acyloxy that the present invention relates to, 2 ��-many halogen is for podophyllotoxin derivative, and its chemical general formula is:
C-2 position chlorine in chemical general formula is substituted by �� configuration, wherein
A, E-2 ' position is that chlorine replaces, and C-4 bit substituent R is respectively:
B, E-2', 6' position is that chlorine replaces, and C-4 bit substituent R is respectively:
C, E-2' position is that bromine replaces, and C-4 bit substituent R is respectively:
4 alpha-acyloxy-2'(2', 6'), 2 ��-many halogen is for the E-ring halogen formed in podophyllotoxin derivative preparation process for C-ring aromatize product, and its structural formula is:
According to 2 ��-chlorine in earlier stage for the insecticidal activity result of study of podophyllotoxin aromatic acid derivative, result shows, series 4 alpha-acyloxy-2 ' (2 ' of the present invention, 6 '), agriculture and forestry injurious insect mythimna separata is had by 2 ��-many halogen for podophyllotoxin derivative stronger refuses food cytotoxicity, can be used for preparing the plant insecticide of high-efficiency low-toxicity.
The following is 4 alpha-acyloxies-2 ' (2 '; 6 '); 2 ��-many halogen is for the preparation method of podophyllotoxin derivative; the method is that raw material goes protection obtained 2 ' (2 ' by E ring halogen generation, C-4 position hydroxyl protection, C-2 position alpha-chloro, C-4 position taking podophyllotoxin; 6 '), 2 ��-many halogen, for podophyllotoxin derivative, finally obtains 4 alpha-acyloxies-2 ' (2 ' with 11 kinds of carboxylic acids and reaction respectively; 6 '), 2 ��-many halogen is for podophyllotoxin derivative.
A, 4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen is for the preparation of podophyllotoxin derivative (1-28):
By appropriate 2 ' (2 ', 6 '), 2 ��-many halogen is dissolved in methylene dichloride for podophyllotoxin, carboxylic acid and appropriate DMAP (DMAP), at room temperature add appropriate dewatering agent N after stirred for several minute, N'-dicyclohexylcarbodiimide (DCC), then room temperature reaction it is placed in, TLC tracing detection, reaction is filtered after terminating, remove dicyclohexylurea (DCU) solid, filtrate adds with dichloromethane extraction after a small amount of water, merges with anhydrous sodium sulfate drying after organic phase, concentrated steam dry after be separated by preparation silica gel thin sheet and to obtain required sterling;
B, 4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen is for the preparation of podophyllotoxin derivative (1-4,12-15,21-24 and 29-31):
By 2 ' appropriate (2 ', 6 '), 2 ��-many halogen is dissolved in q. s. methylene chloride for podophyllotoxin and carboxylic acid, under ice salt is bathed after stirred for several minute, adds appropriate BF3��Et2O, under agitation returns to room temperature, TLC tracing detection, after reaction terminates, adds with dichloromethane extraction after a small amount of water in reaction solution, merges with anhydrous sodium sulfate drying after organic phase, concentrated steam dry after be separated by preparation silica gel thin sheet and to obtain required sterling.
2 ' described (2 ', 6 '), 2 ��-many halogen is for the preparation method of podophyllotoxin derivative:
With concentrated hydrochloric acid and tetrahydrofuran (THF) mixed solvent hydrolysis 2 ' (2 ' that volume ratio is 1/9,6 '), 2 ��-many halogen generation-4-O-tetrahydropyrans podophyllotoxin, TLC tracing detection, after hydrolysis reaction terminates, with 5% sodium bicarbonate neutralization, adjust ph to 5, removing tetrahydrofuran (THF) under reduced pressure, with dichloromethane extraction, the organic phase after merging is washed with 5% sodium bicarbonate and saturated common salt successively, then with anhydrous sodium sulfate drying, being separated to obtain for 2 ' (2 ', 6 ') through silica gel column chromatography after concentrated steaming is dry, 2 ��-many halogen is for podophyllotoxin sterling;
2 ' described (2 ', 6 '), the preparation method of 2 ��-many halogen generation-4-O-tetrahydropyrans podophyllotoxin:
Under nitrogen protection, Diisopropylamine is added drop-wise in the tetrahydrofuran solution of n-Butyl Lithium to prepare lithium diisopropyl amido, it is cooled to-78 DEG C with low-temp reaction device for subsequent use; By 2 ' (2 ', 6 ')-halogen generation-4-O-tetrahydropyrans podophyllotoxin is dissolved in a small amount of dry tetrahydrofuran, then join in lithium diisopropyl amido solution slowly, obtain yellow transparent solution, continue to stir a moment at-78 DEG C, then hexachloroethane is joined in yellow transparent solution, under agitation return to room temperature, TLC tracing detection; Through removing tetrahydrofuran (THF) under reduced pressure when having reacted, with methylene dichloride dilution, successively with water, 0.1mol/L hydrochloric acid, washing, anhydrous sodium sulfate drying, it is separated through silica gel column chromatography after concentrated steaming is dry and to obtain required 2 ' (2 ', 6 '), 2 ��-many halogen generation-4-O-tetrahydropyrans podophyllotoxin sterling;
The preparation method of 2 ' described (2 ', 6 ')-halogen generation-4-O-tetrahydropyrans podophyllotoxin:
Taking 2 ' (2 ', 6 ')-halogen is dissolved in dihydropyrane for podophyllotoxin, drips a phosphorus oxychloride that adds 1, and after dissolving in the water-bath of 60-63 DEG C, stirring at room temperature is reacted, TLC tracing detection. When reaction is substantially complete, after the dihydropyrane that pressure reducing and steaming is unnecessary, obtain 2 ' (2 ', 6 ')-halogen generation-4-O-tetrahydropyrans podophyllotoxin crude product;
2 ' described (2 ', 6 ')-halogen for the preparation method of podophyllotoxin is:
Taking podophyllotoxin is dissolved in anhydrous N, N'-dimethyl formamide, then for succimide, N-chlorosuccinimide or N-bromine is dissolved in anhydrous N, N'-dimethyl formamide, slowly drips in reaction solution, naturally rise to room temperature, TLC tracing detection at 0 DEG C. After reacting completely, being poured in water, extraction into ethyl acetate, after merging organic phase, respectively with sodium carbonate, saturated sodium-chloride washing, anhydrous sodium sulfate drying, after concentrated, column chromatographic isolation and purification obtains 2 ' (2 ', 6 ')-halogen for podophyllotoxin sterling.
Carboxylic acid and alcohol used is respectively:
Glacial acetic acid, propionic acid, naphthylacetic acid, toluylic acid, nicotinic acid, ��-picolinic acid, n-caprylic acid, phenylformic acid, 0-chloro-benzoic acid, meta-toluic acid, m-chlorobenzoic acid are wherein a kind of.
The following is the specific embodiment that contriver provides.
Embodiment 1:
One, product: 4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen refers to following content for podophyllotoxin derivative 1-31(each derivative physico-chemical property)
Two, preparation method:
It is below the synthetic route of 2 ' (2 ', 6 ')-halogen for podophyllotoxin:
Taking podophyllotoxin is dissolved in anhydrous N, N'-dimethyl formamide, then for succimide, N-chlorosuccinimide or N-bromine is dissolved in anhydrous N, N'-dimethyl formamide, slowly drips in reaction solution, naturally rise to room temperature, TLC tracing detection at 0 DEG C. After reacting completely, being poured in water, extraction into ethyl acetate, after merging organic phase, respectively with sodium carbonate, saturated sodium-chloride washing, anhydrous sodium sulfate drying, after concentrated, column chromatographic isolation and purification obtains 2 ' (2 ', 6 ')-halogen for podophyllotoxin sterling.
The physico-chemical property of 2'-chlorine podophyllotoxin is as follows:
1), white solid, fusing point 116-117 DEG C, specific rotatory power [��]20 D=-63(C=3.8mg/mL, chloroform).
2), hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 500MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.08 (s, 1H, H-5), 6.37 (s, 1H, H-8), 6.19 (s, 1H, H-6 '), 5.94 (s, 2H, OCH2O), 5.20 (d, J=4.0Hz, 1H, H-1), 4.79 (d, J=8.5Hz, 1H, H-4), 4.66 (dd, J=8.5Hz, 6.5Hz, 1H, H-11), 4.10 (t, J=9.0Hz, 1H, H-11), 3.91 (s, 3H, 3 '-OCH3), 3.86 (s, 3H, 5 '-OCH3), 3.65 (s, 3H, 4 '-OCH3), 2.93-2.96 (m, 2H, H-2,3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 125MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.9,151.5,150.0,147.9,147.6,142.8,133.5,132.6,131.4,110.6,109.7,105.6,101.4,72.0,70.8,61.1,61.0,56.4,44.2,41.8.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC22H25ClNO8([M+NH4]+), 466.1263; Found, 466.1270.
The physico-chemical property of 2 ', 6 '-two chlorine podophyllotoxin is as follows:
1), white solid, fusing point 159-160 DEG C, specific rotatory power [��]20 D=-30(C=3.3mg/mL, chloroform).
2), hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 500MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.15 (s, 1H, H-5), 6.31 (s, 1H, H-8), 5.94 (d, J=0.5Hz, 2H, OCH2O), 5.52 (d, J=8.5Hz, 1H, H-1), 4.77 (d, J=10.0Hz, 1H, H-4), 4.66 (dd, J=8.5Hz, 7.0Hz, 1H, H-11), 4.08 (dd, J=10.5Hz, 9.0Hz, 1H, H-11), 3.95 (s, 3H, 3 '-OCH3), 3.94 (s, 3H, 5 '-OCH3), 3.80 (s, 3H, 4 '-OCH3), 3.49-3.53 (m, 1H, H-3), 3.01 (dd, J=15Hz, 8.5Hz, 1H, H-2).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 125MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.7,149.4,149.0,147.7,147.4,147.2,132.6,130.9,130.1,129.0,124.1,107.7,105.7,101.3,72.5,70.8,61.2,61.1,61.0,43.8,43.1,39.3.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC22H24Cl2NO8([M+NH4]+), 500.0873; Found, 500.0868.
The physico-chemical property of 2 '-bromine podophyllotoxin is as follows:
1), white solid, fusing point 140-141 DEG C, specific rotatory power [��]20 D=-42(C=3.5mg/mL, chloroform).
2), hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 500MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.08 (s, 1H, H-5), 6.36 (s, 1H, H-8), 6.20 (s, 1H, H-6 '), 5.94 (s, 2H, OCH2O), 5.27 (s, 1H, H-1), 4.78 (d, J=9.0Hz, 1H, H-4), 4.63-4.66 (m, 1H, H-11), 4.10 (t, J=9.0Hz, 1H, H-11), 3.91 (s, 3H, 3 '-OCH3), 3.86 (s, 3H, 5 '-OCH3), 3.64 (s, 3H, 4 '-OCH3), 2.91-2.99 (m, 2H, H-2,3), 2.52 (s, 1H, OH-4).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 125MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 173.0,152.2,150.8,147.8,147.5,142.6,135.5,132.4,131.5,114.4,110.5,109.6,105.6,101.4,71.8,70.9,61.0,56.3,44.0,41.8,41.7.
4), ESI-TRAP source mass spectrum (MS) figure of this compound is characterized as: 515 ([M+Na]+, 100), 517 ([M+Na]+, 98).
It is below the synthetic route of 2 ' (2 ', 6 ')-halogen generation-4-O-tetrahydropyrans podophyllotoxin:
Taking 2 ' (2 ', 6 ')-halogen is dissolved in dihydropyrane for podophyllotoxin, drips a phosphorus oxychloride that adds 1, and stirring at room temperature is reacted, TLC tracing detection. When reaction is substantially complete, after the dihydropyrane that pressure reducing and steaming is unnecessary, obtain 2 ' (2 ', 6 ')-halogen generation-4-O-tetrahydropyrans podophyllotoxin crude product;
It was below 2 ' (2 ', 6 '), the synthetic route of 2 ��-many halogen generation-4-O-tetrahydropyrans podophyllotoxin:
Under nitrogen protection, by 2 ' (2 ', 6 ')-halogen generation-4-O-tetrahydropyrans podophyllotoxin is dissolved in a small amount of dry tetrahydrofuran, then join in lithium diisopropyl amido solution slowly, obtain yellow transparent solution, continue to stir a moment at-78 DEG C, then hexachloroethane is joined in yellow transparent solution, under agitation return to room temperature, TLC tracing detection; Through removing tetrahydrofuran (THF) under reduced pressure when having reacted, with methylene dichloride dilution, successively with water, 0.1mol/L hydrochloric acid, washing, anhydrous sodium sulfate drying, concentrated steams dry required 2 ' (2 ', 6 '), 2 ��-many halogen generation-4-O-tetrahydropyrans podophyllotoxin crude product, is directly used in next step reaction;
Being below 2 ' (2 ', 6 '), 2 ��-many halogen is for the synthetic route of podophyllotoxin:
With concentrated hydrochloric acid and tetrahydrofuran (THF) mixed solvent hydrolysis 2 ' (2 ' that volume ratio is 1/9,6 '), 2 ��-many halogen generation-4-O-tetrahydropyrans podophyllotoxin, TLC tracing detection, after hydrolysis reaction terminates, with 5% sodium bicarbonate neutralization, after adjust ph, removing tetrahydrofuran (THF) under reduced pressure, with dichloromethane extraction, the organic phase after merging is washed with 5% sodium bicarbonate and saturated common salt successively, then with anhydrous sodium sulfate drying, being separated to obtain for 2 ' (2 ', 6 ') through silica gel column chromatography after concentrated steaming is dry, 2 ��-many halogen is for podophyllotoxin sterling;
The physico-chemical property of 2 ', 2 ��-two chlorine podophyllotoxins is as follows:
1), white solid, fusing point 183-184 DEG C, specific rotatory power [��]20 D=-83(C=3.1mg/mL, chloroform).
2), hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.07 (s, 1H, H-5), 6.74 (s, 1H, H-8), 6.62 (s, 1H, H-6 '), 5.92 (dd, J=5.2,1.2Hz, 2H, OCH2O), 5.48 (s, 1H, H-1), 4.90 (d, J=2.8Hz, 1H, H-4), 4.81 (dd, J=9.2,4.8Hz, 1H, H-11), 4.47 (d, J=9.2Hz, 1H, H-11), 3.93 (s, 3H, 3 '-OCH3), 3.88 (s, 3H, 5 '-OCH3), 3.73 (s, 3H, 4 '-OCH3), 3.14-3.16 (m, 1H, H-3), 2.47 (s, 1H, OH).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.3,152.1,149.7,148.7,148.2,142.50,132.3,129.7,128.5,121.5,109.1,107.4,101.5,73.5,73.0,67.0,61.1,61.0,56.3,50.7,45.2.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC22H20O8Cl2Na([M+Na]+), 505.0427; Found, 505.0428.
The physico-chemical property of 2 ', 6 ', 2 ��-trichlorine podophyllotoxin is as follows:
1), white solid, fusing point 92-93 DEG C, specific rotatory power [��]20 D=-104(C=3.9mg/mL, chloroform).
2), hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.04 (s, 1H, H-5), 6.13 (s, 1H, H-8), 5.99 (s, 1H, H-1), 5.90 (dd, J=7.2,1.2Hz, 2H, OCH2O), 4.82 (dd, J=8.8,3.6Hz, 1H, H-11), 4.62 (d, J=9.2Hz, 1H, H-11), 4.43 (d, J=9.2Hz, 1H, H-4), 3.98 (s, 3H, 3 '-OCH3), 3.96 (s, 3H, 5 '-OCH3), 3.82 (s, 3H, 4 '-OCH3), 3.16 (dd, J=9.6,3.6Hz, 1H, H-3), 1.58 (s, 1H, OH).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 173.3,149.4,148.9,147.7,147.5,147.3,134.2,129.6,127.4,127.2,125.9,107.6,104.7,101.3,70.8,69.0,65.6,61.3,61.2,61.1,50.8,44.1.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC22H19O8Cl3Na([M+Na]+), 539.0037; Found, 538.0051.
The physico-chemical property of 2 '-bromo-2 ��-chlorine podophyllotoxin is as follows:
1), white solid, fusing point 170-172 DEG C, specific rotatory power [��]20 D=-94(C=3.4mg/mL, chloroform).
2), hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: 7.10 (s, 1H, H-5), 6.74 (s, 1H, H-8), 6.64 (s, 1H, H-6 '), 5.91 (dd, J=5.2,1.2Hz, 2H, OCH2O), 5.56 (s, 1H, H-1), 4.89 (d, J=2.8Hz, 1H, H-4), 4.81 (dd, J=9.2,4.8Hz, 1H, H-11), 4.47 (d, J=9.2Hz, 1H, H-11), 3.92 (s, 3H, 3 '-OCH3), 3.88 (s, 3H, 5 '-OCH3), 3.72 (s, 3H, 4 '-OCH3), 3.14 (t, J=4.0Hz, 1H, H-3), 2.53 (s, 1H, OH).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.3,152.8,150.7,148.6,148.2,142.4,134.1,129.8,128.4,113.1,109.4,108.9,107.5,101.5,73.4,73.1,67.1,61.04,61.00,56.4,50.7,47.8.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC22H20O8ClBrNa([M+Na]+), 548.9922; Found, 548.9906.
It is below the synthetic route of compound 1-31:
A. the synthetic route of compound 1-28
By 1 equivalent 2 ' (2 ', 6 '), 2 ��-many halogen is dissolved in dry dichloromethane solvent for podophyllotoxin, 1.2 DMAPs working as quantity carboxylic acid and catalytic amount, 1.2 equivalent dewatering agent N are added after stirring at room temperature number minute, N'-dicyclohexylcarbodiimide, then room temperature continues reaction, TLC tracing detection, and reaction is filtered to remove dicyclohexylurea (DCU) solid after terminating. Filtrate adds water, with dichloromethane extraction, with anhydrous sodium sulfate drying after merging organic phase, is separated by preparation silica gel thin sheet after concentrated steaming is dry and to obtain required sterling.
Reaction expression is as follows:
B. the synthetic route of compound 1-4,12-15,21-24 and 29-31:
By 1 equivalent 2'(2', 6'), 2 ��-many halogen is worked as quantity carboxylic acid for podophyllotoxin and 1.2 and is dissolved in q. s. methylene chloride, under ice salt is bathed, adds 1.2 equivalent BF3��Et2After O, under agitation return to room temperature, TLC tracing detection, after reaction terminates, reaction solution add with dichloromethane extraction after water, merge with anhydrous sodium sulfate drying after organic phase, concentrated steam dry after be separated by preparation silica gel thin sheet and to obtain required sterling.
Reaction expression is as follows:
The physico-chemical property of compound 1 is as follows:
1), white solid, fusing point 150-151 DEG C, specific rotatory power [��]20 D=-78(C=3.5mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 500MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 6.68 (s, 1H, H-5), 6.64 (s, 1H, H-8), 6.58 (s, 1H, H-6 '), 5.93-5.95 (m, 3H, H-4, OCH2O), 5.52 (s, 1H, H-1), 4.80-4.81 (m, 2H, H-11), 3.94 (s, 3H, 3 '-OCH3), 3.88 (s, 3H, 5 '-OCH3), 3.76 (s, 3H, 4 '-OCH3), 2.97-2.98 (m, 1H, H-3), 2.16 (s, 3H, COCH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 125MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.9,170.6,152.0,149.9,149.2,148.2,142.6,132.1,130.8,123.9,122.0,108.8,108.6,108.3,101.7,75.1,73.2,66.8,61.14,61.12,56.1,49.3,44.7,21.1.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC24H22O9Cl2Na([M+Na]+), 547.0533; Found, 547.0529.
The physico-chemical property of compound 2 is as follows:
1), white solid, fusing point 179-180 DEG C, specific rotatory power [��]20 D=-80(C=2.9mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 6.67 (s, 1H, H-5), 6.62 (s, 1H, H-8), 6.57 (s, 1H, H-6 '), 5.93-5.94 (m, 3H, OCH2O, H-4), 5.51 (s, 1H, H-1), 4.80-4.81 (m, 2H, H-11), 3.93 (s, 3H, 3 '-OCH3), 3.88 (s, 3H, 5 '-OCH3), 3.75 (s, 3H, 4 '-OCH3), 2.96-2.97 (m, 1H, H-3), 2.35-2.42 (m, 2H, CH3CH 2 ), 1.20 (t, J=7.6Hz, 3H, CH 3 CH2)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 174.2,171.9,152.09,150.02,149.2,148.2,142.8,132.2,130.7,124.2,122.1,108.8,108.6,108.5,101.7,74.9,73.1,66.8,61.12,61.11,56.2,49.4,44.7,27.5,9.0.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC25H24O9Cl2Na([M+Na]+), 561.0689; Found, 561.0691.
The physico-chemical property of compound 3 is as follows:
1), white solid, fusing point 78-80 DEG C, specific rotatory power [��]19 D=-66(C=3.6mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, wherein each peak is attributed to: ��: 7.27-7.39 (m, 5H), 6.67 (s, 1H, H-5), 6.57 (s, 1H, H-8), 6.51 (s, 1H, H-6 '), 5.93 (d, J=1.2Hz, 2H, OCH2O), 5.89 (d, J=3.2Hz, 1H, H-4), 5.50 (s, 1H, H-1), 4.77-4.78 (m, 2H, H-11), 3.93 (s, 3H, 3 '-OCH3), 3.89 (s, 3H, 5 '-OCH3), 3.75 (s, 3H, 4 '-OCH3), 3.67 (d, J=6.8Hz, 2H, PhCH 2 ), 2.994-2.998 (m, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.8,171.6,152.0,150.0,149.2,148.2,142.8,132.6,132.1,130.6,129.0,128.9,127.7,123.9,122.1,108.7,108.6,108.4,101.7,75.5,72.9,66.7,61.13,61.12,56.3,49.2,44.6,41.1.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC30H26O9Cl2Na([M+Na]+), 623.0846; Found, 623.0849.
The physico-chemical property of compound 4 is as follows:
1), white solid, fusing point 92-94 DEG C, specific rotatory power [��]20 D=-56(C=3.2mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.90-7.93 (m, 2H), 7.84-7.86 (m, 1H), 7.53-7.56 (m, 2H), 7.38-7.47 (m, 2H), 6.68 (s, 1H, H-5), 6.55 (s, 1H, H-8), 6.43 (s, 1H, H-6 '), 5.92 (dd, J=6.8,1.2Hz, 2H, OCH2O), 5.87 (d, J=3.2Hz, 1H, H-4), 5.50 (s, 1H, H-1), 4.73 (d, J=2.8Hz, 2H, H-11), 4.12 (d, J=7.2Hz, 2H, C10H7 CH 2 ), 3.94 (s, 3H, 3 '-OCH3), 3.89 (s, 3H, 5 '-OCH3), 3.72 (s, 3H, 4 '-OCH3), 2.99 (dd, J=6.0,2.8Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.8,171.7,152.0,150.0,149.2,148.2,142.8,133.9,132.2,131.7,130.6,129.3,129.1,128.7,127.9,126.8,126.1,125.5,123.9,123.0,122.1,108.7,108.3,101.7,75.5,72.8,66.7,61.14,61.12,56.3,49.2,44.6,39.0.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC34H28O9Cl2Na([M+Na]+), 673.1002; Found, 673.0973.
The physico-chemical property of compound 5 is as follows:
1), white solid, fusing point 156-158 DEG C, specific rotatory power [��]20 D=-79(C=3.0mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 6.67 (s, 1H, H-5), 6.61 (s, 1H, H-8), 6.57 (s, 1H, H-6 '), 5.93 (dd, J=3.6,0.8Hz, 2H, OCH2O), 5.91 (d, J=3.2Hz, 1H, H-4), 5.51 (s, 1H, H-1), 4.80-4.81 (m, 2H, H-11), 3.93 (s, 3H, 3 '-OCH3), 3.88 (s, 3H, 5 '-OCH3), 3.74 (s, 3H, 4 '-OCH3), 2.95-2.96 (m, 1H, H-3), 2.32-2.38 (m, 2H), 1.67-1.70 (m, 2H), 1.29-1.33 (m, 8H), 0.87-0.90 (m, 3H).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 173.6,171.9,152.0,150.0,149.2,148.2,142.7,132.2,130.7,124.2,122.1,108.8,108.6,108.5,101.7,74.8,73.1,66.8,61.13,61.12,56.2,49.4,44.7,34.2,31.6,29.1,28.8,24.9,22.5,14.0.
The physico-chemical property of compound 6 is as follows:
1), white solid, fusing point 89-90 DEG C, specific rotatory power [��]20 D=-52(C=2.8mg/mL, chloroform);
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.994-8.01 (m, 2H), 7.62 (t, J=7.2Hz, 1H), 7.45 (t, J=7.6Hz, 2H), 6.746 (s, 1H, H-5), 6.742 (s, 1H, H-8), 6.65 (s, 1H, H-6 '), 5.98 (d, J=2.8Hz, 1H, H-4), 5.96 (s, 2H, OCH2O), 5.58 (s, 1H, H-1), 5.02 (d, J=9.6Hz, 1H, H-11), 4.88 (dd, J=9.6,4.8Hz, 1H, H-11), 3.93 (s, 3H, 3 '-OCH3), 3.84 (s, 3H, 5 '-OCH3), 3.41 (s, 3H, 4 '-OCH3), 3.16 (t, J=3.6Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.1,167.0,152.1,150.0,149.3,148.3,142.9,133.9,132.3,130.9,129.7,129.0,128.6,123.9,122.1,108.9,108.7,101.7,76.4,73.3,66.8,61.1,61.0,56.5,49.4,44.6.
The physico-chemical property of compound 7 is as follows:
1), white solid, fusing point 80-82 DEG C, specific rotatory power [��]20 D=-71(C=3.3mg/mL, chloroform);
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.72 (d, J=7.6Hz, 1H), 7.35-7.49 (m, 3H), 6.81 (s, 1H, H-5), 6.65 (s, 1H, H-8), 6.63 (s, 1H, H-6 '), 6.09 (d, J=4.0Hz, 1H, H-4), 5.97 (s, 2H, OCH2O), 5.57 (s, 1H, H-1), 4.98 (d, J=9.6Hz, 1H, H-11), 4.90 (d, J=9.6Hz, 1H, H-11), 3.91 (s, 3H, 3 '-OCH3), 3.81 (s, 3H, 5 '-OCH3), 3.143-3.149 (m, 4H, H-3,4 '-OCH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.0,166.1,152.1,149.9,149.5,148.3,142.6,133.4,133.3,132.0,131.3,131.1,131.0,129.5,126.9,123.3,121.9,109.0,108.9,108.2,101.8,73.3,66.8,61.1,61.0,55.5,49.4,44.8.
The physico-chemical property of compound 8 is as follows:
1), white solid, fusing point 84-85 DEG C, specific rotatory power [��]20 D=-45(C=3.3mg/mL, chloroform);
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.916-7.959 (m, 2H), 7.604-7.63 (m, 1H), 7.42-7.45 (m, 1H), 6.71 (s, 1H, H-5), 6.69 (s, 1H, H-8), 6.64 (s, 1H, H-6 '), 6.01 (d, J=3.2Hz, 1H, H-4), 5.973 (d, J=1.2Hz, 2H, OCH2O), 5.57 (s, 1H, H-1), 4.98 (d, J=9.6Hz, 1H, H-11), 4.86 (dd, J=9.6,4.4Hz, 1H, H-11), 3.93 (s, 3H, 3 '-OCH3), 3.85 (s, 3H, 5 '-OCH3), 3.50 (s, 3H, 4 '-OCH3), 3.13 (t, J=3.6Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.9,165.7,152.1,150.1,149.5,148.4,143.1,134.8,134.0,132.2,130.9,130.7,130.0,129.6,127.9,123.6,122.2,109.0,108.9,108.5,101.8,76.6,73.1,66.7,61.1,61.0,56.6,49.3,44.6.
The physico-chemical property of compound 9 is as follows:
1), white solid, fusing point 94-96 DEG C, specific rotatory power [��]20 D=-44(C=3.4mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.792-7.797 (m, 2H), 7.43 (d, J=7.6Hz, 1H), 7.33 (t, J=7.6Hz, 1H), 6.73 (s, 2H, H-5, H-8), 6.65 (s, 1H, H-6 '), 5.974-5.976 (m, 3H, H-4, OCH2O), 5.58 (s, 1H, H-1), 5.03 (d, J=9.2Hz, 1H, H-11), 4.88 (dd, J=9.2,4.4Hz, 1H, H-11), 3.93 (s, 3H, 3 '-OCH3), 3.84 (s, 3H, 5 '-OCH3), 3.41 (s, 3H, 4 '-OCH3), 3.14-3.16 (m, 1H, H-3), 2.14 (s, 3H, CH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.1,167.1,152.2,150.0,149.3,148.3,142.9,138.6,134.7,132.3,130.9,130.1,128.9,128.5,126.9,124.0,122.1,108.9,108.78,108.74,101.7,76.2,73.3,66.9,61.1,61.0,56.5,49.4,44.6,21.2.
The physico-chemical property of compound 10 is as follows:
1), white solid, fusing point 88-90 DEG C, specific rotatory power [��]20 D=-40(C=3.2mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: 9.214 (d, J=1.6Hz, 1H), 8.853-8.869 (m, 1H), 8.29-8.327 (m, 1H), 7.44-7.47 (m, 1H), 6.73 (s, 2H, H-5, H-8), 6.64 (s, 1H, H-6 '), 6.05 (d, J=3.2Hz, 1H, H-4), 5.97 (s, 2H, OCH2O), 5.57 (s, 1H, H-1), 4.97 (d, J=9.6Hz, 1H, H-11), 4.88 (dd, J=9.6,4.8Hz, 1H, H-11), 3.93 (s, 3H, 3 '-OCH3), 3.85 (s, 3H, 5 '-OCH3), 3.50 (s, 3H, 4 '-OCH3), 3.16 (t, J=3.6Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.9,165.5,154.3,152.1,150.8,150.1,149.5,148.4,143.2,137.2,132.1,130.9,125.1,123.5,123.4,122.4,109.5,109.0,108.5,101.8,73.0,66.7,61.1,61.0,56.8,49.3,44.6.
The physico-chemical property of compound 11 is as follows:
1), white solid, fusing point 179-180 DEG C, specific rotatory power [��]20 D=-42(C=2.9mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: 8.83 (d, J=6.0Hz, 2H), 7.83 (dd, J=4.8,1.6Hz, 2H), 6.72 (s, 2H, H-5, H-8), 6.65 (s, 1H, H-6 '), 6.05 (d, J=3.2Hz, 1H, H-4), 5.97 (s, 2H, OCH2O), 5.57 (s, 1H, H-1), 4.95 (d, J=9.2Hz, 1H, H-11), 4.87 (dd, J=9.6,4.8Hz, 1H, H-11), 3.93 (s, 3H, 3 '-OCH3), 3.87 (s, 3H, 5 '-OCH3), 3.86 (s, 3H, 4 '-OCH3), 3.15 (t, J=3.2Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.8,165.5,152.1,150.8,150.2,149.6,148.4,143.4,136.4,132.0,131.0,123.2,122.7,122.6,109.8,109.0,108.5,101.8,72.9,66.6,61.1,61.0,57.0,49.3,44.6.
The physico-chemical property of compound 12 is as follows:
1), white solid, fusing point 92-93 DEG C, specific rotatory power [��]19 D=-86(C=3.3mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 6.51 (s, 1H, H-5), 6.23 (s, 1H, H-8), 6.07 (s, 1H, H-1), 5.92-5.93 (m, 3H, OCH2O, H-4), 4.76-4.78 (m, 1H, H-11), 4.57-4.59 (m, 1H, H-11), 3.98 (s, 3H, 3 '-OCH3), 3.96 (s, 3H, 5 '-OCH3), 3.83 (s, 3H, 4 '-OCH3), 3.39-3.41 (m, 1H, H-3), 2.24 (s, 3H, COCH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.8,171.1,149.3,148.9,148.1,147.6,147.4,133.3,127.5,125.9,125.5,107.8,105.7,101.5,71.2,70.9,64.9,61.3,61.28,61.20,48.9,44.1,21.1.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC24H21O9Cl3Na([M+Na]+), 581.0143; Found, 581.0150.
The physico-chemical property of compound 13 is as follows:
1), white solid, fusing point 84-86 DEG C, specific rotatory power [��]19 D=-107(C=2.8mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 6.49 (s, 1H, H-5), 6.23 (s, 1H, H-8), 6.07 (s, 1H, H-1), 5.90-5.93 (m, 3H, OCH2O, H-4), 4.75 (dd, J=7.2,3.2Hz, 1H, H-11), 4.58 (d, J=7.6Hz, 1H, H-11), 3.98 (s, 3H, 3 '-OCH3), 3.96 (s, 3H, 5 '-OCH3), 3.83 (s, 3H, 4 '-OCH3), 3.38 (dd, J=5.6,2.8Hz, 1H, H-3), 2.49-2.52 (m, 2H, COCH 2 CH3), 1.23 (t, J=6.0Hz, 3H, COCH2CH 3 )��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 174.4,172.8,149.3,149.0,148.1,147.6,147.4,133.3,127.5,126.1,125.5,107.8,105.8,101.4,71.3,70.9,65.0,61.3,61.2,61.1,49.1,44.1,27.7,9.1.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC25H23O9Cl3Na([M+Na]+), 595.0299; Found, 595.0300.
The physico-chemical property of compound 14 is as follows:
1), white solid, fusing point 78-80 DEG C, specific rotatory power [��]19 D=-95(C=2.8mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.31-7.37 (m, 5H), 6.34 (s, 1H, H-5), 6.21 (s, 1H, H-8), 6.05 (s, 1H, H-1), 5.885 (dd, J=10.0,1.2Hz, 2H, OCH2O), 5.86 (d, J=7.2Hz, 1H, H-4), 4.65 (dd, J=9.2,4.0Hz, 1H, H-11), 4.46 (d, J=9.6Hz, 1H, H-11), 3.97 (s, 3H, 3 '-OCH3), 3.95 (s, 3H, 5 '-OCH3), 3.83 (s, 3H, 4 '-OCH3), 3.76 (s, 2H, PhCH 2), 3.31 (dd, J=7.2,3.6Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.7,171.6,149.2,148.9,148.1,147.6,147.3,133.2,133.1,129.2,128.8,127.6,127.5,127.5,125.8,125.5,107.7,105.8,101.4,71.6,71.1,64.9,61.3,61.2,61.1,49.0,44.1,41.5.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC30H25O9Cl3Na([M+Na]+), 657.0456; Found, 657.0424.
The physico-chemical property of compound 15 is as follows:
1), white solid, fusing point 88-90 DEG C, specific rotatory power [��]20 D=-84(C=3.1mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 8.02 (d, J=8.4Hz, 1H), 7.883-7.90 (m, 1H), 7.82-7.85 (m, 1H), 7.462-7.59 (m, 4H), 6.32 (s, 1H, H-5), 6.18 (s, 1H, H-8), 6.01 (s, 1H, H-1), 5.873 (dd, J=9.2,1.2Hz, 2H, OCH2O), 5.84 (d, J=7.2Hz, 1H, H-4), 4.53 (dd, J=9.6,4.0Hz, 1H, H-11), 4.38 (d, J=9.2Hz, 1H, H-11), 4.220 (d, J=0.4Hz, 2H, C10H7CH 2 ), 3.97 (s, 3H, 3 '-OCH3), 3.94 (s, 3H, 5 '-OCH3), 3.82 (s, 3H, 4 '-OCH3), 3.19 (dd, J=7.2,4.0Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.7,171.7,149.2,148.9,148.1,147.5,147.3,133.9,133.1,131.8,129.7,128.9,128.5,128.3,127.5,127.4,126.6,126.0,125.7,125.5,123.4,107.7,106.0,101.4,71.9,71.2,64.7,61.3,61.2,61.1,49.0,44.0,39.4.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC34H27O9Cl3Na([M+Na]+), 707.0612; Found, 707.0640.
The physico-chemical property of compound 16 is as follows:
1), white solid, fusing point 88-90 DEG C, specific rotatory power [��]20 D=-77(C=2.9mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 8.084-8.10 (m, 2H), 7.62 (t, J=7.6Hz, 1H), 7.48-7.54 (m, 2H), 6.59 (s, 1H, H-5), 6.27 (s, 1H, H-8), 6.19 (d, J=6.8Hz, 1H, H-4), 6.13 (s, 1H, H-1), 5.901 (dd, J=9.6,1.2Hz, 2H, OCH2O), 4.79 (dd, J=9.2,4.0Hz, 1H, H-11), 4.74 (d, J=9.2Hz, 1H, H-11), 3.99 (s, 3H, 3 '-OCH3), 3.97 (s, 3H, 5 '-OCH3), 3.85 (s, 3H, 4 '-OCH3), 3.54-3.57 (m, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.8,166.5,149.3,149.0,148.2,147.6,147.5,133.8,133.2,130.7,130.0,129.1,128.7,128.5,127.66,127.61,126.6,126.1,107.8,106.0,101.5,71.7,71.4,64.9,61.3,61.27,61.23,49.2,44.2.
The physico-chemical property of compound 17 is as follows:
1), white solid, fusing point 90-91 DEG C, specific rotatory power [��]20 D=-94(C=3.3mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.891-7.91 (m, 1H), (7.495-7.515 m, 2H), 7.363-7.40 (m, 1H), 6.63 (s, 1H, H-5), 6.26 (s, 1H, H-8), 6.22 (d, J=7.2Hz, 1H, H-4), 6.12 (s, 1H, H-1), 5.91 (s, 2H, OCH2O), 4.82 (dd, J=9.2,4.0Hz, 1H, H-11), 4.75 (d, J=9.2Hz, 1H, H-11), 3.98 (s, 3H, 3 '-OCH3), 3.96 (s, 3H, 5 '-OCH3), 3.83 (s, 3H, 4 '-OCH3), 3.58-3.61 (m, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.7,165.7,149.3,149.0,148.3,147.6,147.5,134.2,133.3,133.2,131.7,131.4,128.9,127.66,127.62,126.9,125.7,125.5,107.9,106.0,101.5,72.4,71.4,64.8,61.3,61.2,61.1,49.0,44.1.
The physico-chemical property of compound 18 is as follows:
1), white solid, fusing point 92-94 DEG C, specific rotatory power [��]20 D=-94(C=3.6mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.87-7.91 (m, 2H), 7.44 (d, J=7.6Hz, 1H), 7.36 (t, J=7.6Hz, 1H), 6.58 (s, 1H, H-5), 6.26 (s, 1H, H-8), 6.17 (d, J=7.2Hz, 1H, H-4), 6.13 (s, 1H, H-1), 5.89-5.90 (m, 2H, OCH2O), 4.78 (dd, J=9.6,4.0Hz, 1H, H-11), 4.70 (d, J=9.6Hz, 1H, H-11), 3.99 (s, 3H, 3 '-OCH3), 3.97 (s, 3H, 5 '-OCH3), 3.85 (s, 3H, 4 '-OCH3), 3.54-3.56 (m, 1H, H-3), 2.44 (s, 3H, CH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.9,166.7,149.3,149.0,148.1,147.6,147.4,138.6,134.6,133.3,130.5,128.9,128.6,127.63,127.60,127.1,126.1,125.5,107.8,106.0,101.4,71.4,71.3,65.0,61.3,61.27,61.22,49.2,44.2,21.3.
The physico-chemical property of compound 19 is as follows:
1), white solid, fusing point 89-90 DEG C, specific rotatory power [��]20 D=-79(C=3.9mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 8.05-8.06 (m, 1H), 7.96 (d, J=7.6Hz, 1H), 7.602-7.627 (m, 1H), 7.43 (t, J=8.0Hz, 1H), 6.56 (s, 1H, H-5), 6.28 (s, 1H, H-8), 6.17 (d, J=7.2Hz, 1H, H-4), 6.13 (s, 1H, H-1), 5.911 (dd, J=7.6,1.2Hz, 2H, OCH2O), 4.79 (dd, J=9.2,4.0Hz, 1H, H-11), 4.70 (d, J=9.6Hz, 1H, H-11), 3.99 (s, 3H, 3 '-OCH3), 3.97 (s, 3H, 5 '-OCH3), 3.85 (s, 3H, 4 '-OCH3), 3.54-3.57 (m, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.7,165.4,149.3,149.0,148.3,147.6,147.5,134.9,133.8,133.1,130.8,130.08,130.01,128.1,127.7,127.6,125.6,125.4,107.9,105.9,101.5,72.2,71.3,64.8,61.3,61.27,61.24,49.2,44.2.
The physico-chemical property of compound 20 is as follows:
1), white solid, fusing point 80-81 DEG C, specific rotatory power [��]20 D=-101(C=3.0mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 9.30 (s, 1H), 8.92-8.93 (m, 1H), 8.61 (d, J=7.6Hz, 1H), 7.72-7.75 (m, 1H), 6.55 (s, 1H, H-5), (6.30 s, 1H, H-8), 6.23 (d, J=6.0Hz, 1H, H-4), 6.13 (s, 1H, H-1), 5.94 (s, 2H, OCH2O), 4.83-4.85 (m, 1H, H-11), 4.73-4.75 (m, 1H, H-11), 3.99 (s, 3H, 3 '-OCH3), 3.97 (s, 3H, 5 '-OCH3), 3.85 (s, 3H, 4 '-OCH3), 3.57-3.60 (m, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.57,163.5,149.6,149.3,149.1,148.7,147.77,147.75,147.0,141.5,132.7,128.0,127.6,125.4,125.3,124.6,108.0,106.1,101.7,73.8,71.4,64.5,61.3,61.2,49.2,44.1.
The physico-chemical property of compound 21 is as follows:
1), white solid, fusing point 176-178 DEG C, specific rotatory power [��]20 D=-94(C=3.4mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 6.71 (s, 1H, H-5), 6.63 (s, 1H, H-8), 6.60 (s, 1H, H-6 '), 5.93-5.95 (m, 3H, OCH2O, H-4), 5.59 (s, 1H, H-1), 4.80-4.81 (m, 2H, H-11), 3.92 (s, 3H, 3 '-OCH3), 3.88 (s, 3H, 5 '-OCH3), 3.76 (s, 3H, 4 '-OCH3), 2.97 (dd, J=5.2,2.8Hz, 1H, H-3), 2.15 (s, 3H, COCH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.9,170.6,152.7,150.9,149.2,148.2,142.6,133.9,130.9,123.9,113.7,108.76,108.73,108.6,101.7,75.1,73.1,66.8,61.08,61.00,56.2,49.4,47.3,21.0.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC24H22O9ClBrNa([M+Na]+), 591.0028; Found, 591.0028.
The physico-chemical property of compound 22 is as follows:
1), white solid, fusing point 169-170 DEG C, specific rotatory power [��]20 D=-83(C=3.2mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 6.71 (s, 1H, H-5), 6.62 (s, 1H, H-8), 6.60 (s, 1H, H-6 '), 5.930-5.943 (m, 3H, OCH2O, H-4), 5.59 (s, 1H, H-1), 4.80-4.81 (m, 2H, H-11), 3.92 (s, 3H, 3 '-OCH3), 3.88 (s, 3H, 5 '-OCH3), 3.75 (s, 3H, 4 '-OCH3), 2.96-2.98 (m, 1H, H-3), 2.35 (q, J=7.6Hz, 2H, COCH 2CH3), 1.20 (t, J=7.6Hz, 3H, COCH2CH 3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 174.2,171.9,152.7,150.9,149.2,148.2,142.7,134.0,130.8,124.1,113.7,108.9,108.7,108.5,101.7,74.8,73.1,66.8,61.08,61.00,56.2,49.4,47.2,27.5,9.0.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC25H24O9ClBrNa([M+Na]+), 605.0184; Found, 605.0169.
The physico-chemical property of compound 23 is as follows:
1), white solid, fusing point 88-90 DEG C, specific rotatory power [��]20 D=-68(C=3.6mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, wherein each peak is attributed to: ��: 7.280-7.39 (m, 5H), 6.70 (s, 1H, H-5), 6.59 (s, 1H, H-8), 6.51 (s, 1H, H-6 '), 5.937 (d, J=0.8Hz, 2H, OCH2O), 5.88 (d, J=3.2Hz, 1H, H-4), 5.58 (s, 1H, H-1), 4.78-4.79 (m, 2H, H-11), 3.92 (s, 3H, 3 '-OCH3), 3.88 (s, 3H, 5 '-OCH3), 3.75 (s, 3H, 4 '-OCH3), 3.67 (d, J=7.2Hz, 2H, PhCH 2 ), 2.990 (dd, J=5.2,3.2Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.8,171.6,152.7,151.0,149.2,148.2,142.7,133.9,132.6,130.8,129.0,128.9,127.7,123.8,113.8,108.9,108.6,108.3,101.7,75.4,72.9,66.8,61.09,61.01,56.3,49.3,47.2,41.1.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC30H26O9ClBrNa([M+Na]+), 667.0341; Found, 667.0320.
The physico-chemical property of compound 24 is as follows:
1), white solid, fusing point 90-92 DEG C, specific rotatory power [��]20 D=-67(C=3.7mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.90-7.94 (m, 2H), 7.84 (d, J=7.6Hz, 1H), 7.540-7.57 (m, 2H), (7.39-7.48 m, 2H), 6.71 (s, 1H, H-5), 6.58 (s, 1H, H-8), 6.43 (s, 1H, H-6 '), 5.931 (dd, J=6.0,1.2Hz, 2H, OCH2O), 5.87 (d, J=3.2Hz, 1H, H-4), 5.57 (s, 1H, H-1), 4.741 (d, J=2.8Hz, 2H, H-11), 4.12 (d, J=7.2Hz, 2H, C10H7CH 2 ), 3.92 (s, 3H, 3 '-OCH3), 3.88 (s, 3H, 5 '-OCH3), 3.72 (s, 3H, 4 '-OCH3), 2.99 (dd, J=6.0,1.2Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.78,171.75,152.7,151.0,149.2,148.2,142.8,133.98,133.95,131.7,130.7,129.3,129.1,128.7,127.9,126.8,126.1,125.5,123.7,123.0,113.8,109.0,108.6,108.3,101.7,75.4,72.7,66.7,61.08,61.00,56.3,49.2,47.1,39.0.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC34H28O9ClBrNa([M+Na]+), 717.0497; Found, 717.0505.
The physico-chemical property of compound 25 is as follows:
1), white solid, fusing point 160-162 DEG C, specific rotatory power [��]20 D=-53(C=3.2mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.994-8.01 (m, 2H), 7.620-7.65 (m, 1H), 7.45 (t, J=7.6Hz, 2H), 6.77 (s, 1H, H-5), 6.74 (s, 1H, H-8), 6.68 (s, 1H, H-6 '), 5.97 (d, J=2.8Hz, 1H, H-4), 5.96 (s, 2H, OCH2O), 5.66 (s, 1H, H-1), 5.03 (d, J=9.2Hz, 1H, H-11), 4.88 (dd, J=9.2,4.8Hz, 1H, H-11), 3.91 (s, 3H, 3 '-OCH3), 3.84 (s, 3H, 5 '-OCH3), 3.41 (s, 3H, 4 '-OCH3), 3.16 (t, J=3.6Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.0,167.0,152.8,151.0,149.3,148.3,142.9,134.1,133.9,131.0,129.7,129.0,128.8,128.6,123.8,113.8,109.1,108.8,108.6,101.7,76.3,73.3,66.9,61.03,61.00,56.5,49.4,47.2.
The physico-chemical property of compound 26 is as follows:
1), white solid, fusing point 84-85 DEG C, specific rotatory power [��]20 D=-71(C=3.0mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.72-7.73 (m, 1H), 7.487-7.51 (m, 2H), 7.33-7.37 (m, 1H), 6.81 (s, 1H, H-5), 6.69 (s, 1H, H-8), 6.65 (s, 1H, H-6 '), 6.101 (d, J=2.8Hz, 1H, H-4), 5.966-5.975 (m, 2H, OCH2O), 5.65 (s, 1H, H-1), 4.97 (d, J=9.2Hz, 1H, H-11), 4.89 (dd, J=9.6,4.4Hz, 1H, H-11), 3.90 (s, 3H, 3 '-OCH3), 3.81 (s, 3H, 5 '-OCH3), 3.14-3.16 (m, 4H, H-3,4 '-OCH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.9,166.1,152.8,150.9,149.5,148.3,142.6,133.8,133.4,133.2,131.4,131.1,131.0,129.6,126.8,123.2,113.6,109.0,108.8,108.6,101.7,73.3,66.8,60.9,55.6,49.4,47.4.
The physico-chemical property of compound 27 is as follows:
1), white solid, fusing point 88-89 DEG C, specific rotatory power [��]20 D=-50(C=3.1mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.78-7.797 (m, 2H), 7.43 (d, J=8.0Hz, 1H), 7.33 (t, J=8.0Hz, 1H), 6.76 (s, 1H, H-5), 6.73 (s, 1H, H-8), 6.68 (s, 1H, H-6 '), 5.96-5.977 (m, 3H, H-4, OCH2O), 5.66 (s, 1H, H-1), 5.03 (d, J=9.2Hz, 1H, H-11), 4.88-4.91 (m, 1H, H-11), 3.91 (s, 3H, 3 '-OCH3), 3.84 (s, 3H, 5 '-OCH3), 3.41 (s, 3H, 4 '-OCH3), 3.151-3.16 (m, 1H, H-3), 2.41 (s, 3H, CH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 172.0,167.1,152.8,150.9,149.3,148.3,142.8,138.6,134.7,134.1,131.0,130.1,128.9,128.5,126.9,123.8,113.7,109.0,108.78,108.70,101.7,76.2,73.3,66.9,61.03,61.00,56.4,49.4,47.2,21.2.
The physico-chemical property of compound 28 is as follows:
1), white solid, fusing point 98-100 DEG C, specific rotatory power [��]20 D=-47(C=3.4mg/mL, chloroform).
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 400MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.91-7.959 (m, 2H), 7.605-7.632 (m, 1H), 7.42 (t, J=8.0Hz, 1H), 6.72 (s, 1H, H-5), 6.71 (s, 1H, H-8), 6.67 (s, 1H, H-6 '), 6.01 (d, J=3.2Hz, 1H, H-4), 5.97 (s, 2H, OCH2O), 5.65 (s, 1H, H-1), 4.99 (d, J=9.6Hz, 1H, H-11), 4.87 (dd, J=9.6,4.8Hz, 1H, H-11), 3.92 (s, 3H, 3 '-OCH3), 3.85 (s, 3H, 5 '-OCH3), 3.49 (s, 3H, 4 '-OCH3), 3.13 (t, J=3.6Hz, 1H, H-3).
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 100MHz) feature: taking deuterochloroform as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 171.9,165.7,152.8,151.0,149.4,148.4,143.0,134.9,134.03,134.01,131.0,130.7,130.0,129.6,127.9,123.4,113.9,109.3,108.8,108.5,101.8,76.5,73.1,66.7,61.04,61.01,56.6,49.3,47.1.
The physico-chemical property of compound 29 is as follows:
1), white solid, fusing point 168-169 DEG C.
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 500MHz) feature: taking deuterated dimethyl sulfoxide as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 8.01 (s, 1H), (7.56 s, 1H), 6.77 (s, 1H), 6.71 (s, 1H), 6.20 (s, 2H, OCH2O), 5.44-5.53 (m, 2H, H-11), 3.90 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 3.74 (s, 3H, OCH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 125MHz) feature: taking deuterated dimethyl sulfoxide as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 168.8,151.8,149.7,149.1,148.6,142.3,140.0,135.2,134.2,129.4,128.7,120.1,118.8,118.3,109.9,130.7,102.1,101.5,68.2,60.9,60.6,56.0.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC22H17O7ClNa([M+Na]+), 451.0555; Found, 451.0570.
The physico-chemical property of compound 30 is as follows:
1), white solid, fusing point 218-219 DEG C.
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 500MHz) feature: taking deuterated dimethyl sulfoxide as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 8.05 (s, 1H), 7.58 (s, 1H), 6.75 (s, 1H), 6.22 (s, 2H, OCH2O), 5.53 (s, 2H, H-11), 4.02 (s, 3H, 4 '-OCH3), 3.89 (s, 6H, 3 ', 5 '-OCH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 125MHz) feature: taking deuterated dimethyl sulfoxide as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 168.8,149.9,149.1,148.8,147.5,140.1,134.5,132.3,128.5,128.2,122.7,120.8,118.8,103.9,102.27,100.7,68.5,61.2,61.0.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC22H16O7Cl2Na([M+Na]+), 485.0165; Found, 485.0170.
The physico-chemical property of compound 31 is as follows:
1), white solid, fusing point 237-238 DEG C.
2), this compound hydrogen nuclear magnetic resonance collection of illustrative plates (1HNMR, 500MHz) feature: taking deuterated dimethyl sulfoxide as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 7.74 (s, 1H), (7.22 s, 1H), 6.84 (s, 1H), 6.59 (s, H), 6.09 (s, 2H, OCH2O), 5.35-5.45 (m, 2H, H-11), 4.01 (s, 3H, OCH3), 3.98 (s, 3H, OCH3), 3.79 (s, 3H, OCH3)��
3), nuclear magnetic resonance of carbon collection of illustrative plates (13CNMR, 125MHz) feature: taking deuterated dimethyl sulfoxide as solvent, TMS is interior mark, and wherein each peak is attributed to: ��: 169.2,152.7,151.1,150.1,148.9,143.0,139.7,138.4,134.6,131.5,129.7,119.6,119.3,110.3,109.7,103.8,103.0,101.9,68.3,61.28,61.24,56.1.
4), ESI-TRAP source high resolution mass spectrum (HRMS) figure of this compound is characterized as: CalcdforC22H18O7Br([M+H]+), 473.0230; Found, 473.0235.
Embodiment 2: raw survey is tested
1, for examination insect: 3 ages are armyworm larvae in earlier stage, provides by insectary, Xibei Univ. of Agricultural & Forest Science & Technology's public nuisance-free agricultural chemicals research centre.
2, sample and reagent:
Sample is: Toosendanin, podophyllotoxin, 2 '-chlorine podophyllotoxin, 2 ', 6 '-two chlorine podophyllotoxin, 2 '-bromine podophyllotoxin, 2 ', 2 ��-two chlorine podophyllotoxins, 2 ', 6 ', 2 ��-trichlorine podophyllotoxin, 2 '-bromo-2 ��-chlorine podophyllotoxin and compound 1-31. Solvent is acetone, Chengdu Ke Long chemical reagent factory, analytical pure.
3, sod cultivation:
Adopt little leaf butterfly additive process: be bottom the culture dish of 9 centimetres, spread a metafiltration paper at diameter, and the moisturizing that adds water. Every ware is chosen and is got armyworm larvae in earlier stage in 10 3 in the same size, more healthy and stronger ages. Take 5mg Toosendanin, podophyllotoxin, 2 '-chlorine podophyllotoxin, 2 ' respectively, 6 '-two chlorine podophyllotoxin, 2 '-bromine podophyllotoxin, 2 ', 2 ��-two chlorine podophyllotoxins, 2 ', 6 ', 2 ��-trichlorine podophyllotoxin, 2 '-bromo-2 ��-chlorine podophyllotoxin and compound 1-31, add 5ml acetone, it is made into the liquid that concentration is 1mg/ml. The leaflet dish that oat leaf is cut into 1 �� 1 centimetre, soaks 3 seconds in liquid to be measured, feeds examination worm after drying. Take acetone solution as blank group. Often process 10, repeat 3 times. Under room temperature (about 25 DEG C), humidity 65%��80%, light application time raise when being 12 hours/12 hours. Feed with normal blade after 48 hours until sprouting wings. The food ingestion of periodic logging insect, survivor of a murder attempt's number, reveal any symptoms etc., try the worm anti-food rate of 24 hours, 48 hours and final mortality ratio according to following formulae discovery. Measurement result is in table 1. Anti-food rate (%)=(the average average food ingestion of food ingestion-treatment group of control group)/(the average food ingestion of control group) �� 100
Final mortality ratio (%)=(the dead number of examination worm)/(the examination total number of worm) �� 100
Correct mortality ratio (%)=(process mortality ratio-comparison mortality ratio)/(1-compares mortality ratio) �� 100
Table 1: compound involved in the present invention to 3 ages early stage mythimna separata refuse food toxic effect
Conclusion: result shows, 2 '-chlorine podophyllotoxin, 2 ' prepared by the present invention, 6 '-two chlorine podophyllotoxin, 2 '-bromine podophyllotoxin, 2 ', 2 ��-two chlorine podophyllotoxins, 2 ', 6 ', in 2 ��-trichlorine podophyllotoxin, 2 '-bromo-2 ��-chlorine podophyllotoxin and compound 1-31, compound 2 '-chlorine podophyllotoxin, 2 ', 6 '-two chlorine podophyllotoxin, 2 '-bromo-2 ��-chlorine podophyllotoxin, 6,7,14,19,26,27 and 30 show with commercialization agricultural chemicals Toosendanin mortality ratio quite or higher activity. In synthesized 37 compounds, wherein mortality ratio higher than or be equivalent to parent compound podophyllotoxin have 33.

Claims (1)

1.2 ' (2 ', 6 ')-many halogen is for the application of podophyllotoxin derivative for the preparation of plant insecticide, and described 2 ' (2 ', 6 ')-many halogen for the structural formula of podophyllotoxin derivative is:
CN201310521288.2A 2013-10-28 2013-10-28 4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen is for podophyllotoxin derivative and Synthesis and applications Expired - Fee Related CN103554125B (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4567253A (en) * 1984-02-03 1986-01-28 Tony Durst 2-Substituted derivatives of podophyllotoxin and etoposide
CN1332165A (en) * 2001-02-27 2002-01-23 西北农林科技大学无公害农药研究服务中心 Podophyllotoxin compound and its application in pesticide
CN101575342A (en) * 2009-03-30 2009-11-11 西北农林科技大学 2beta-chloropodophyllotoxin aromatic acid ester compounds, preparation and application in preparing botanical pesticide
CN102093382A (en) * 2011-02-14 2011-06-15 西北农林科技大学 2alpha or 2beta-bromopodophyllotoxin derivatives, preparation thereof, and application thereof to botanical pesticides

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4567253A (en) * 1984-02-03 1986-01-28 Tony Durst 2-Substituted derivatives of podophyllotoxin and etoposide
CN1332165A (en) * 2001-02-27 2002-01-23 西北农林科技大学无公害农药研究服务中心 Podophyllotoxin compound and its application in pesticide
CN101575342A (en) * 2009-03-30 2009-11-11 西北农林科技大学 2beta-chloropodophyllotoxin aromatic acid ester compounds, preparation and application in preparing botanical pesticide
CN102093382A (en) * 2011-02-14 2011-06-15 西北农林科技大学 2alpha or 2beta-bromopodophyllotoxin derivatives, preparation thereof, and application thereof to botanical pesticides

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Insight into dihalogenation of E-ring of podophyllotoxins, and their acyloxyation derivatives at the C4 position as insecticidal agents;Zhiping Che，等;《Bioorganic & Medicinal Chemistry Letters》;20130817;第23卷(第20期);第5592-5598页 *
Natural products-based insecticidal agents 4. Semisynthesis and insecticidal activity of novel esters of 2-chloropodophyllotoxin against Mythimna separate Walker in vivo;Hui Xu，等;《Bioorganic & Medicinal Chemistry Letters》;20090728;第19卷(第18期);第5415-5418页 *
Synthesis of Novel 4α-(Acyloxy)-2’(2’,6’)-(di)halogenopodophyllotoxin Derivatives as Insecticidal Agents;Zhiping Che，等;《Journal of Agricultural and Food Chemistry》;20130805;第61卷(第34期);第8148-8155页，尤其参见第8149页图1，左栏第2段-右栏第2段，第8150页合成路线1，第8154页表1，右栏第一段 *

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