CN104945354A - Split-ring polyoxy-substituted cyclohexene compound and application thereof - Google Patents
Split-ring polyoxy-substituted cyclohexene compound and application thereof Download PDFInfo
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- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/16—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by esterified hydroxyl radicals
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Abstract
The invention belongs to the field of natural drugs, and relates to a novel-structure split-ring polyoxy-substituted cyclohexene compound artabotrol A separated from Artabotrys pilosus branch and leaf. Multiple in-vitro activity screening indicates that the compound has obvious antitumor activity, has equivalent protein tyrosine kinase inhibition activity to the positive control drug, has the prospects in developing targeted antineoplastic drugs by using the protein tyrosine kinase as the target, is applicable to antineoplastic drugs, has the advantages of simple separation and purification technique and mild reaction conditions, and has practical meanings.
Description
Technical field
The invention belongs to natural medicine field, relate to a kind of driffractive ring Polyoxygenated cyclohexenes compounds and application thereof, specifically a kind of derive from mao leaf Artabotrys odoratissimus there is the driffractive ring Polyoxygenated cyclohexenes compounds of novel structure and the application in antitumor drug thereof.
Background technology
Along with tumour mechanism continuous is illustrated and being constantly found of antitumor action target spot, Mutiple Targets Tumor suppression signal transduction becomes the important directions of new type antineoplastic medicine exploitation.Relative to single target drug and multiple single target drug drug combination, Mutiple Targets medicine has more superiority.Mutiple Targets medicine can effectively be avoided producing the interaction between medicine, reduces untoward reaction, the therapeutic action advantage such as more comprehensively.In various molecular target, protein tyrosine kinase (protein tyrosine kinase, PTK) be current effect the most obviously and one of the most wide antitumor drug action target spot of application prospect.PTK is the enzyme system of one group of catalytic proteins tyrosine residues phosphorylation, it plays a very important role in intracellular signal transduction, closely related with the growth of tumour cell, propagation, differentiation and apoptosis, by suppressing PTK can tumoricidal signal transmission, inhibition tumor cell is bred, thus reaches antineoplastic object.Existing multiple tyrosine kinase inhibitor series antineoplastic medicament goes on the market or enters clinical study at present, and achieves good clinical efficacy, as anti-tumor drugs targetings such as imatinibs.
Annonaceae (Annonaceae) claws of a hawk Pittosporum (Artabotrys) plant, be generally climbing shrub plant, the whole world about has 100 kinds, be distributed in subtropical and tropical zones, China produces 4 kinds, i.e. hair leaf Artabotrys odoratissimus (A.pilosus Merr.et Chun), narrow lobe Artabotrys odoratissimus (A.hainanensis R.E.Fries), Artabotrys hongkongensis flower (A.hongkongensis Hance) and Artabotrys odoratissimus (A.hexapetalus (L.f.) Bhandari), be distributed in the west and south to the southeast, wherein hair leaf Artabotrys odoratissimus and narrow lobe Artabotrys odoratissimus be Hainan Native Plants [Chinese Plants will editorial committee of the Chinese Academy of Sciences. Chinese Plants will. the 30th volume. Science Press. Beijing: 1979, p121-128.].Among the people, Artabotrys odoratissimus platymiscium makes the existing very long history of medicinal plant, has clearing heat and detoxicating, effect of anti-inflammatory analgetic, is commonly used for treatment malaria and incidence lymphoid tuberculosis etc.Modern pharmacology research shows, this platymiscium has biological activity widely, as antitumor, antibacterial, antimalarial and desinsection isoreactivity [Gu Guanyun; Jiang Yu. the research overview III of annonaceae vegetable cell poison composition. external medicine (plant amedica fascicle), 1995,10:153-156.; Radloff P.D, Philipps J, Nkeyi M, et al.Arteflene compared with mefloquine for treating Plasmodium falciparum malaria in children.American Journal of Tropical Medicine and Hygiene, 1996,55:259-262.; Singh D.K, Basha S.A, Sarma, B.K, et al.Antifungal activity of a phytoterpenoid (AOS-A) isolated from Artabotrytis odoratissimus on spore germination of some fungi.Mycobiology, 2006,34:120-123.; Srivastava B, Singh P, Srivastava A.K, et al.Efficacy of Artabotrys odoratissimus oil as a plant based antimicrobial against storage fungi and a flatoxin B1 secretion.International Journal of Food Science and Technology, 2009,44:1909-1915.; Tattersfield F, Potter C.The insecticidal properties of certain species of Annona and of an Indian strain of Mundulea sericea.Annals of Applied Biology, 1940,27:262-273.].Just because of this, for many years, this platymiscium enjoys the favor of vegetalization educational circles and pharmacology educational circles, from this genus various plants, a large amount of type of isolation identification is extremely enriched and has extensive bioactive compound so far, as alkaloid compound [Zhou Q, Fu Y.H, Li X.B, et al.Bioactive benzylisoquinoline alkaloids from Artabotrys hexapetalus.Phytochemistry Lett.2015,11:296-300., Sichaem J, Ruksilp T, Worawalai W, et al.A new dimeric aporphine from the roots of Artabotrys spinosus.Fitoterapia 2011,82:422-425.], terpenoid [Gupta C, Prasad S, Sahai M, et al.Artabotryols A-E, New Lanostane Triterpenes from the Seeds of Artabotrys odoratissimus.Helv.Chim.Act.2010,93:1925-1932., Zhang L, Zhou W.S, Xu X.X.et al.A new sesquiterpene peroxide (yingzhaosu C) and sesquiterpenol (yingzhaosu D) from Artabotrys unciatus (L.) Meer.J.Chem.Soc., Chem.Commun.1988, 8:523-524.], butyrolactone compound [Wong H.F, Brown, G.D. β-Methoxy-γ-methylene-α, β-unsaturated-γ-butyrolactones from Artabotrys hexapetalus.Phytochemistry, 2002, 59:99-104.] and flavonoid compound [Li T.M, Li W.K, Yu J.G.Flavonoids from Artabotrys hexapetalus.Phytochemistry 1997, 45:831-833., Singh A.P, Sahai M.Isolation of flavonol glycosides from the leaves of Artabotrys odoratissmus.Planta med.1996,62:192-194.] etc. various structures type compound.
Driffractive ring Polyoxygenated cyclohexenes compounds is the type of compounds that a class is extremely rare, distribution phyto-group is extremely narrow, mainly be distributed in annonaceae Uvaria microcarpa platymiscium, up to now only report 7 the type compound [Chen Z, Liu Y.L, Xu Q.M.et al.New polyoxygenated cyclohexene and polyoxygenated seco-cyclohexene from Uvaria boniana.J.Asian Nat.Prod.Res.2013,15,53-58.; Zhang C.R, Wu Y, Yue J.M.Chin.J.Nat.Med.2010,8,84-87.; Wang S, Chen R.Y, Yu S.S.et al.Uvamalols D-G:novel polyoxygenated seco-cyclohexenes from the roots of Uvaria macrophylla.J.Asian Nat.Prod.Res.2003,5,17-23.; Lu Y.P, Mu Q, Zheng H.L.et al.Two new constituents from Uvaria microcarpa.Chin.Chem.Lett.1995,6,775-778.].
((A.pilosus) is annonaceae Artabotrys odoratissimus platymiscium to hair leaf Artabotrys odoratissimus, is often born in low altitude area in the mountain region woods of intermediate altitude, is China's endemic plant, is only distributed in Hainan Island.Early stage, preliminary study found, the ethanol extraction of hair leaf Artabotrys odoratissimus has good HIV (human immunodeficiency virus)-resistant activity [He J.J, Park I.W, Chen G.Y.et al.Extracts of medicinal plant and uses thereof.PCT Int.Appl.2011, WO 2011014561 A1 20110203.], in addition, chemical composition and bioactive research report thereof in relevant hair leaf Artabotrys odoratissimus is showed no at present both at home and abroad.
Summary of the invention
The object of this invention is to provide a kind of driffractive ring Polyoxygenated cyclohexenes compounds and application thereof, is from hair leaf Artabotrys odoratissimus branches and leaves, be separated the driffractive ring Polyoxygenated cyclohexenes compounds artabotrol A with novel structure obtained.The screening of multiple external activity shows: this compound has the inhibit activities of significant anti-tumor activity and the protein tyrosine kinase suitable with positive control drug, and can be developed further into protein tyrosine kinase is the antitumor drug of target.
The chemical structure of driffractive ring Polyoxygenated cyclohexenes compounds artabotrol A provided by the present invention is as follows:
A separation purification method of separation and purification compound a rtabotrol A from hair leaf Artabotrys odoratissimus branches and leaves, its detailed step comprises:
A. hair leaf Artabotrys odoratissimus branches and leaves methyl alcohol or 95% ethanolic soln are extracted 3 times, filter, collect filtrate, then concentrating under reduced pressure is dry, obtain alcohol extract;
B. alcohol extract is added water and make suspension, extract by sherwood oil and ethyl acetate successively, acetic acid ethyl acetate extract concentrating under reduced pressure, obtain extraction into ethyl acetate medicinal extract;
C. extraction into ethyl acetate medicinal extract is carried out column chromatography separating purification, obtain monomeric compound artabotrol A.
Further, the step C of above-mentioned preparation method comprises: 1, by the extraction into ethyl acetate medicinal extract silica gel column chromatography section of drawing, difference 20:1 by volume, 10:1,5:1,1:1 carry out sherwood oil-acetone gradient elution, and collected volume is than the eluate of the sherwood oil-acetone for 10:1; 2, get sherwood oil-acetone (volume ratio 10:1) eluate and remove pigment through MCI resin column chromatography, 30:70,50:50,70:30 carry out methanol-water gradient elution by volume respectively, and collected volume is than the eluate of the methanol-water for 70:30; 3, get methanol-water (volume ratio 70:30) eluate and carry out reversed-phase silica gel column chromatography, 60:40,65:45,70:30 carry out methanol-water gradient elution by volume, and collected volume concentrates than the eluate of the methanol-water for 60:40; 4, get methanol-water (volume ratio 60:40) eluate preparative high performance liquid chromatography to be separated, moving phase is the acetonitrile-water of volume ratio 35:65, obtains monomeric compound artabotrol A.
Compound a rtabotrol A provided by the present invention shows through multiple external activity screening: this compound has the inhibit activities of significant anti-tumor activity and the protein tyrosine kinase suitable with positive control drug, can be used for the application preparing with protein tyrosine kinase the anti-tumor drugs targeting being target.
Present invention process is simple, with hair leaf Artabotrys odoratissimus branches and leaves for raw material extracts the driffractive ring Polyoxygenated cyclohexenes compounds with novel structure, show that this compound has significant anti-tumor activity through multiple external activity screening, can apply in antitumor drug, there is realistic meaning.
Embodiment
Below in conjunction with embodiment, the specific embodiment of the present invention is described in further detail.Following examples for illustration of the present invention, but are not used for limiting the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually conveniently experiment condition.
Embodiment one: the separation and purification of compound a rtabotrol A
Get a mao dried powder for leaf Artabotrys odoratissimus branches and leaves (40.0kg, Hainan) and extract 3 times with 95% ethanolic soln cold soaking, each extraction one week, filters, and collect filtrate, concentrating under reduced pressure obtains ethanol extraction 1280.0g, added water by this alcohol extract and make suspension, use sherwood oil and extraction into ethyl acetate successively, acetic acid ethyl acetate extract, through concentrating under reduced pressure, obtains acetic acid ethyl ester extract 380.0g, acetic acid ethyl ester extract is carried out column chromatography separating purification: by the segmentation of extraction into ethyl acetate medicinal extract silica gel column chromatography, sherwood oil-acetone gradient elution (20:1, 10:1, 5:1, 1:1), collect sherwood oil-acetone (volume ratio 10:1) eluate, get sherwood oil-acetone (volume ratio 10:1) eluate MCI resin column chromatography and remove pigment, with methanol-water gradient elution (volume ratio 30:70, 50:50, 70:30), collect methanol-water (volume ratio 70:30) eluate, get methanol-water (volume ratio 70:30) eluate and carry out reversed-phase silica gel column chromatography, with (volume ratio 60:40, 65:45, 70:30), collect methanol-water (volume ratio 60:40) eluate to concentrate, get methanol-water (volume ratio 60:40) eluate preparative high performance liquid chromatography to be separated, moving phase is that acetonitrile-water (volume ratio 35:65) obtains pure compound a rtabotrol A (368mg).
Structural identification: by the integration analysis of the various modern spectroscopic techniques such as optical rotational activity spectrum, UV spectrum, infrared spectra, nuclear magnetic resonance spectrum and mass spectrum, determine the chemical structure of compound a rtabotrol A.White amorphous powder,
uV (CH
3oH) λ
max(log ε) 227 (4.72), 274 (3.68), 283 (3.10) nm; IR (KBr) v
max: 3402,3025,2934,2852,1726,1705,1592,1454,1319,1278,1118,1086,711cm
-1;
1h NMR (400MHz, CDCl
3) and
13c NMR (100MHz, CDCl
3) data are in table 1; HR-ESIMS m/z 369.1342 (M+H; Calcd for C
23h
23o
7, 369.1338).
NMR data (the CDCl of table 1 compound 1
3)
| Position | δ H(J in Hz) a | δ C b |
| 1a | 4.48(1H,dd,J＝11.6,3.9Hz) | 68.1t |
| 1b | 4.36(1H,dd,J＝11.6,6.8Hz) | |
| 2 | 5.70(1H,overlap) | 69.9d |
| 3 | 6.06(1H,dd,J＝15.6,5.4Hz) | 128.7d |
| 4 | 5.67(1H,dd,J＝15.6,7.5Hz) | 134.3d |
| 5 | 3.42(1H,dd,J＝7.3,2.4Hz) | 55.6d |
| 6 | 3.24(1H,m) | 57.4d |
| 7a | 4.64(1H,dd,J＝12.4,3.3Hz) | 64.4t |
| 7b | 4.27(1H,dd,J＝12.4,5.8Hz) | |
| 1′ | 129.6s | |
| 1″ | 129.6s | |
| 2′,6′ | 8.06(2H,d,J＝7.5Hz) | 129.7d |
| 2″,6″ | 8.02(2H,d,J＝7.5Hz) | 129.8d |
| 3′,5′ | 7.46(2H,dd,J＝7.5,7.5Hz) | 128.5d |
| 3″,5″ | 7.45(2H,dd,J＝7.5,7.5Hz) | 128.5d |
| 4′ | 7.58(1H,m) | 133.3d |
| 4″ | 7.57(1H,m) | 133.3d |
| 7′ | 166.8s | |
| 7″ | 166.3s |
aMeasured at 400MHz.
bMeasured at 100MHz.
The separation purification method of embodiment two, compound a rtabotrol A
The dried powder (5.0kg, Hainan) of hair leaf Artabotrys odoratissimus branches and leaves extracts 3 times with methyl alcohol cold soaking, each 3 days, and filter, collect filtrate, concentrating under reduced pressure obtains ethanol extraction (172.0g).Methanol extract is added water and makes suspension, use sherwood oil and extraction into ethyl acetate successively, acetic acid ethyl acetate extract concentrating under reduced pressure, obtain acetic acid ethyl ester extract 58.0g, acetic acid ethyl ester extract is carried out column chromatography separating purification: by the segmentation of ethyl acetate extract medicinal extract silica gel column chromatography, sherwood oil-acetone gradient elution (20:1, 10:1, 5:1, 1:1), collect sherwood oil-acetone (volume ratio 10:1) eluate, get sherwood oil-acetone (volume ratio 10:1) eluate MCI resin column chromatography and remove pigment, with methanol-water gradient elution (volume ratio 30:70, 50:50, 70:30), collect methanol-water (volume ratio 70:30) eluate, get methanol-water (volume ratio 70:30) eluate and carry out reversed-phase silica gel column chromatography, with (volume ratio 60:40, 65:45, 70:30), collect methanol-water (volume ratio 60:40) eluate to concentrate, get methanol-water (volume ratio 60:40) eluate preparative high performance liquid chromatography to be separated, moving phase is that acetonitrile-water (volume ratio 35:65) obtains monomeric compound II (52.8mg).
The structural identification of Compound II per: white amorphous powder; HR-ESIMS shows [M+H] of Compound II per
+for m/z 369.1345; The compound a rtabotrol A that Compound II per and embodiment one obtain is TLC altogether, under three kinds of expansion systems, [sherwood oil-acetone (3:1), petroleum ether-ethyl acetate (1:1) and chloroform-acetone (9:1)] is homogeneous spot, illustrates that this compound and compound a rtabotrol A are same compound.
Embodiment three: the antitumor activity of compound a rtabotrol A
1, experimental technique: by four kinds of kinds of tumor cell cycling inhibiting, SPCA-1, SGC-7901 and BEL-7402 use the RPMI-1640 substratum containing 10% calf serum respectively, at 37 DEG C, 5%CO
2cultivate in incubator.Adopt mtt assay to carry out cell inhibitory effect test, be mainly operating as: the tumor cell line in vegetative period of taking the logarithm, with the tryptic digestion of 0.25%, the RPMI-1640 nutrient solution of 10% newborn calf serum is modulated into 5 × 10
4the cell suspension of individual/mL, is inoculated in 96 orifice plates, and 180 μ L are inoculated in every hole.At 37 DEG C, 5%CO
2cultivate 8-10h under saturated humidity condition, treat that it is adherent, each hole adds the sample liquid with PBS preparation, makes sample final concentration be respectively 0.1,1, and 10 μ g/mL.Parallel 3 holes of each concentration, after continuing to cultivate 44h, every hole adds 50 μ L MTT (1mg/mL
-1, PBS prepares), at 37 DEG C, 5%CO
2incubation 4h is continued under condition, culture supernatant in hole is abandoned in suction, every hole adds 150 μ L DMSO, microoscillator shakes up 15min, after dissolving crystallized, enzyme-linked immunosorbent assay instrument selects 570nm, measure the light absorption value in each hole, blank group (only adding celliferous nutrient solution) and control group (with nutrient solution alternative medicine) are set simultaneously, calculate cell proliferation inhibition rate.Inhibiting rate (%)=(OD value mean value/control group 3 hole, 1-experimental group 3 hole OD value mean value) × 100%.Make ordinate zou with inhibiting rate, make regression curve, calculate sample IC
50value.SPSS13.0 statistical package is adopted to carry out data processing and statistical study.
2, anti-tumor activity experimental result
The compound a rtabotrol A obtained by embodiment one to selected tumor cell line K562, the proliferation inhibition activity of the equal showed different of SPCA-1, SGC-7901 and BEL-7402.The results are shown in Table 2.
The anti-tumor activity of table 2 compound a rtabotrol A
Embodiment four: the arrestin tyrosine kinase activity of compound a rtabotrol A
The extraction of PTKs in rat cerebral tissue: taken out by rat brain, rejects meninx, weighs, add the cooled homogenate liquid of 4 times amount.Glass homogenizer high-speed homogenization is used in ice bath, centrifugal, collect supernatant liquor, more centrifugal 10min.Collect supernatant liquor, containing endochylema type tyrosine kinase in supernatant liquor, and precipitation can be used as receptor type tyrosine kinase use.Leave and take the assay of a small amount of supernatant liquor for protein in extract, all the other packing, be placed in-70 DEG C and save backup.
Enzyme plate bag quilt: substrate dilution is added (every hole 125 μ L) in 96 hole enzyme plates, 37 DEG C of overnight incubation.Remove excess substrate liquid in plate, add phosphate buffered saline buffer (PBS-Tween 20) washing, in 37 DEG C of dry 2h.4 DEG C save backup.
Ptk inhibitor screens: first add in enzyme plate by sample, hatch for 37 DEG C, adds the ATP with the dilution of kinase buffer liquid, hatches for 37 DEG C, remove the reaction solution in plate, washing; Add antibody complex, hatch for 37 DEG C; Remove antibody complex in plate, washing, adds tetramethyl benzidine (TMB) nitrite ion, and room temperature lucifuge is reacted, and adds stop buffer, measures absorbancy (A) value in 450nm wavelength place.Positive control drug is imatinib.Inhibiting rate by following formulae discovery compound a rtabotrol A: inhibiting rate %=(A
normally-A
sample)/(A
normally-A
blank) * 100%.
Test gained inhibiting rate is 72.68%, result shows, compound a rtabotrol A has significant restraining effect (inhibiting rate 72.68%) to protein tyrosine kinase, and the inhibit activities of inhibit activities and positive control drug imatinib quite (inhibiting rate 69.32%).
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the prerequisite not departing from the technology of the present invention principle; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (5)
1. a driffractive ring Polyoxygenated cyclohexenes compounds artabotrol A, is characterized in that, its chemical structure is as follows:
2. the separation purification method of compound a rtabotrol A according to claim 1, it is characterized in that, its detailed step comprises:
A. by hair leaf Artabotrys odoratissimus branches and leaves methyl alcohol or 95% ethanolic soln room temperature or heating extraction 3 times, filter, collect filtrate, then concentrating under reduced pressure is dry, obtain alcohol extract;
B. alcohol extract is added water and make suspension, extract by sherwood oil and ethyl acetate successively, acetic acid ethyl acetate extract concentrating under reduced pressure, obtain extraction into ethyl acetate medicinal extract;
C. extraction into ethyl acetate medicinal extract is carried out column chromatography separating purification, obtain monomeric compound artabotrol A.
3. method according to claim 2, it is characterized in that: the detailed step of step C comprises: 1), by the extraction into ethyl acetate medicinal extract silica gel column chromatography section of drawing, difference 20:1 by volume, 10:1,5:1,1:1 carries out sherwood oil-acetone gradient elution, and collected volume is than the eluate of the sherwood oil-acetone for 10:1; 2), get sherwood oil-acetone eluate through MCI resin column chromatography removal pigment, 30:70,50:50,70:30 carry out methanol-water gradient elution by volume respectively, and collected volume is than the eluate of the methanol-water for 70:30; 3), get methanol-water eluate and carry out reversed-phase silica gel column chromatography, 60:40,65:45,70:30 carry out methanol-water gradient elution by volume, and collected volume concentrates than the eluate of the methanol-water for 60:40; 4), get methanol-water eluate preparative high performance liquid chromatography and be separated, moving phase is the acetonitrile-water of volume ratio 35:65, obtains monomeric compound artabotrol A.
4. compound a rtabotrol A according to claim 1 is preparing the application in antitumor drug.
5. compound a rtabotrol A according to claim 1 is preparing with protein tyrosine kinase the application in the anti-tumor drugs targeting being target.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012063985A2 (en) * | 2010-11-12 | 2012-05-18 | 김용문 | Hamburger for cholesterol reduction and manufacturing method therefor |
| CN102724990A (en) * | 2009-07-29 | 2012-10-10 | 印第安纳大学研究及科技有限公司 | Extracts of medicinal plant and uses thereof |
| US20130017187A1 (en) * | 2009-10-15 | 2013-01-17 | Sungshin Women's University Industry-Academic Cooperation Foundation | Pharmacological composition whereby statin and coq10 compounds are enhanced |
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| US20130017187A1 (en) * | 2009-10-15 | 2013-01-17 | Sungshin Women's University Industry-Academic Cooperation Foundation | Pharmacological composition whereby statin and coq10 compounds are enhanced |
| WO2012063985A2 (en) * | 2010-11-12 | 2012-05-18 | 김용문 | Hamburger for cholesterol reduction and manufacturing method therefor |
Non-Patent Citations (6)
| Title |
|---|
| ALLAN PATRICK G. MACABEO ET AL: "Benzoylated derivatives from Uvariarufa", 《BIOCHEMICAL SYSTEMATICS AND ECOLOGY》 * |
| QI ZHOU ET AL: "Bioactive benzylisoquinoline alkaloids from Artabotrys hexapetalus", 《PHYTOCHEMISTRY LETTERS》 * |
| YUPING LU ET AL: "Two New Constituents from UVARIA Microcarpa", 《CHINESE CHEMICAL LETTERS》 * |
| ZHANG CHUAN-RUI ET AL: "Polyoxygenated Seco-cyclohexene Derivatives from Uvaria tonkinensis var. subglabra", 《CHINESE JOURNAL OF NATURAL MEDICINES》 * |
| 刘艳萍 等: "毛叶鹰爪花中一个新颖的裂环多氧取代环己烯类化合物", 《有机化学》 * |
| 韩长日 等: "狭瓣鹰爪花挥发油的化学成分研究", 《中草药》 * |
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