CN110003230A - Crow alkane type diterpenoid and its pharmaceutical composition and its application - Google Patents
Crow alkane type diterpenoid and its pharmaceutical composition and its application Download PDFInfo
- Publication number
- CN110003230A CN110003230A CN201910321049.XA CN201910321049A CN110003230A CN 110003230 A CN110003230 A CN 110003230A CN 201910321049 A CN201910321049 A CN 201910321049A CN 110003230 A CN110003230 A CN 110003230A
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- China
- Prior art keywords
- structural formula
- alkane type
- crow alkane
- preparation
- diterpenoid
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
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- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/20—Spiro-condensed systems
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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Abstract
The invention discloses the Crow alkane type diterpenoids as shown in structural formula (1) and (2), using it as the pharmaceutical composition of effective component, preparation method and its application in preparation treatment or prevention type-2 diabetes mellitus and hyperlipidemia related drugs and health food.Pharmacological activity test proves: the compound of the present invention 1 and 2 can significantly reduce type-2 diabetes mellitus C57BL/KsJdb/db mouse blood sugar, improve the sugar tolerance and insulin tolerance of db/db mouse, and significantly reduce serum levels of triglyceride content.
Description
Technical field:
The invention belongs to technical field of pharmaceuticals, and in particular to Crow alkane type diterpenoid 1 or 2, using it as effective component
Pharmaceutical composition, preparation method and its in preparation treat or prevent type-2 diabetes mellitus and hyperlipidemia and health care
Application in food.
Background technique:
Metabolic syndrome is to be dyslipidemia, pathoglycemia, obesity, fatty liver, hypertension, high blood clotting, II type glycosuria
The glycometabolism of the performance characteristics such as disease, atherosclerosis, nonalcoholic fatty liver, disorders of lipid metabolism syndrome.As economy is sent out
Exhibition and people life style change, and the diabetes as caused by metabolic syndrome and cardiovascular disease incidence rate sharply increase.Glycosuria
Disease is a kind of chronic incretion metabolism disease, and wherein type-2 diabetes mellitus accounts for 90%, and China diabetic has 20,000,000 or more, and
And there is the characteristics of multiple, rejuvenation, seriously threaten national health.The cardinal symptom of type 2 diabetes patient be hyperglycemia,
Hyperlipidemia and insulin resistance etc., this is also to lead to cataract, infection, fatty liver, cardiovascular disease, diabetes, or even dead
Die the main reason for equal.Diabetes have seriously affected people's lives quality, cause a large amount of health care costs.Therefore,
Except through moving the control with diet, the drug for finding treatment diabetes is still the hot spot of current study of pharmacy.
The bioactive natural product for separating and finding in plant resources, is widely used in various disease treatments for many years.It is medicinal
Plant and natural products monomer have been successfully applied to blood glucose control in many countries, also have become and safely and effectively drop
One of the important sources of sugared drug.
Salvia is a kind of important medicinal plant, and especially Radix Salviae Miltiorrhizae is widely applied always throughout our country, is had
It activates blood circulation and disperses blood clots, active logical numbness, mental-tranquilization, detoxify cool blood, swelling and pain relieving and other effects.Pharmacological experiment confirms Radix Salviae Miltiorrhizae quinones
Close object have the effects that anti-inflammatory, coronary dilatation, anti-platelet aggregation, in recent years again have some new pharmacological activity it is for example antitumor, elimination
Free radical isoreactivity is found (Wu, Y.B. in succession；Ni,Z.Y.；Shi,Q.W.；Dong,M.；Kiyota,H.；Gu,Y.C.；
Cong,B.,Chem.Rev.,2012,112(11),5967).Chia (Salvia hispanica) is Labiatae rat-tail
Grass belongs to annual herb plant, and the entitled Chia of English (odd sub-) originates in Mexico south and Guatemala is northern.Gorgon euryale Europe rat-tail
The seed of grass is also known as odd sub- seed, with long edible and medicinal history (Joseph, C.P.,
Genet.Resour.Crop.Ev.2004,51(7),773).In addition to directly eating, also it is used for the food such as biscuit, bread, Yoghourt
The production of product.Sub- seed odd simultaneously also can be used as nutrition fortifier and food additives.China is in the odd sub- seed of approval in 2014
New raw-food material.Studies have shown that rich in multiple proteins, mineral element, vitamin, the serial how unsaturated rouge of ω -3 in odd Asia seed
The ingredients such as fat acid and antioxidant have and maintain horizontal normal lipid, antitumor, anti-oxidant, improvement diabetes and cardiovascular disease
The effects of sick, is widely used in medicine, food, cosmetics etc. (Poudyal, H.；Panchal,S.K.；Waanders,
J.；Ward,L.；Brown,L.,J.Nutr.Bichem.2012,23(2),153)(Taga,M.S.；Miller,E.E.；
Pratt,D.E.,.Am.Oil Chem.Soc.1984,61(5),928).Although odd Asia seed has multiple biological activities and research
Extensively, but the rare report of the chemical component of its aboveground vegetation part.Compound 1 and 2 is Crow alkane type diterpenoid, wherein
Compound 1 is noval chemical compound, and the active function of 2 compounds is without report.
Summary of the invention:
It is an object of the invention to: 2 Crow alkane type diterpenoids are provided, using it as the pharmaceutical composition of active constituent
Object, preparation method and such compound and pharmaceutical composition are in preparation treatment or prevention type-2 diabetes mellitus and hyperlipemia
Drug and health food in application.Pharmacological activity test proves that the compound of the present invention 1 and 2 can significantly reduce II type glycosuria
Sick C57BL/KsJdb/db mouse blood sugar, improves the sugar tolerance and insulin tolerance of db/db mouse, and significantly reduces serum glycerol
Three rouge contents.
In order to realize above-mentioned purpose of the invention, the present invention provides the following technical solutions:
Crow alkane type diterpenoid 1 shown in following structural formula (1),
Crow alkane type diterpenoid 1 or 2 shown in following structural formula treats or prevents type-2 diabetes mellitus and height in preparation
Application in the drug of pionemia,
Crow alkane type diterpenoid 1 or 2 treats or prevents the health food of type-2 diabetes mellitus and hyperlipidemia in preparation
In application.
Pharmaceutical composition, wherein containing Crow alkane type diterpenoid 1 or 2 and pharmaceutically acceptable carrier.
The preparation method of Crow alkane type diterpenoid 1 or 2, comprises the following steps that: taking chia (Salvia
Hispanica aerial part) shines dry doubling and crushes, and is extracted three times with acetone cold soaking, merges extracting solution three times, is concentrated under reduced pressure, obtain
To total medicinal extract, which examines through TLC and knows, according to principal spot through silica gel column chromatography (petroleum ether/acetone, 9:1,8:2,7:3,6:4)
Merged, obtains 5 components.The 5th inverted medium pressure liquid chromatography of component (MPLC MCI) is separated, with ethyl alcohol water system
Gradient elution (70:30,75:25,80:20,85:15,90:10 and 95:5) through combining data detection at 5 inferior components (Fr.5.1~
F.5.5).Component Fr.5.1 obtains compound 1 through the long-term a large amount of crystal of precipitation of placing.4th component is through silica gel column chromatography (petroleum
Ether/chloroform/ethyl acetate, 4:4:1) obtain compound 2.
The fasting blood-glucose of mouse is administered by significantly reducing for Crow alkane type diterpenoid 1 and 2, improves db/db mouse sugar
Tolerance and insulin tolerance reduce serum levels of triglyceride content and realize that it treats or prevents type-2 diabetes mellitus and hyperlipemia in preparation
Application in disease drug and health food.
Pharmaceutically acceptable carrier recited above refers to the pharmaceutical carrier of pharmaceutical field routine, for example, water, grape
Sugar, lactose, Arabic gum etc. and it is suitble to used in the preparation for preparing solid, semisolid, liquid or aerosol form other
Carrier.In addition composition can contain stabilizer, thickener and/or colorant and fragrance.
The composition that Crow alkane type diterpenoid of the invention and its pharmaceutically acceptable carrier are prepared can be through
Mouth is administered without mouth, and dosage is had nothing in common with each other because of drug difference, and for adult, daily 1-100mg is appropriate.
When oral administration, make first compound and conventional medicinal adjuvant such as excipient, solution agent, binder, lubricant,
The mixing such as antioxidant, coating agent, colorant, aromatic, surfactant, is made into the forms such as granule, capsule, tablet
Administration: it can be administered in the form of injection, infusion solution or suppository etc. when non-oral administration.When preparing above-mentioned preparation, it can be used conventional
Preparation technique.
Detailed description of the invention:
Fig. 1 is the structural schematic diagram of Crow alkane type diterpenoid of the invention；
Fig. 2 is the single crystal X diffraction structural schematic diagram of the compound of the present invention 1；
Fig. 3 each group mouse weight change curve:
Fig. 4 each group mouse blood sugar measurement result schematic diagram:
Fig. 5 0GTT curve and area under the curve schematic diagram:
Fig. 6 ITT curve and area under the curve schematic diagram:
Fig. 7 each group mice serum index of correlation measurement result schematic diagram.
Specific embodiment:
With reference to the accompanying drawing, essentiality content of the invention is further illustrated with the embodiment of the present invention, but not with
This limits the present invention.The improvement that essence according to the present invention carries out the present invention belongs to the scope of the present invention.
Embodiment 1:
The preparation method and Structural Identification of Crow alkane type diterpenoid 1 and 2:
Preparation method: taking the aerial part of chia (Salvia hispanica) to shine dry doubling and crush, cold with acetone
Extraction takes three times, merges extracting solution three times, is concentrated under reduced pressure, obtains total medicinal extract, the medicinal extract through silica gel column chromatography (petroleum ether/acetone,
9:1,8:2,7:3,6:4), it examines and knows through TLC, merged according to principal spot, obtain 5 components.The inverted middle hydraulic fluid of 5th component
Phase chromatography (MPLC MCI) is separated, with ethyl alcohol water system gradient elution (70:30,75:25,80:20,85:15,90:10 and
95:5) through combining data detection at 5 inferior components (Fr.5.1~F.5.5).Component Fr.5.1 is obtained through the long-term a large amount of crystal of precipitation of placing
Compound 1.4th component obtains compound 2 through silica gel column chromatography (petroleum ether/chloroform/ethyl acetate, 4:4:1).
Structural Identification: molecular structure of compounds formula (1) of the present invention and (2) respectively correspond compound 1 and 2:
Compound 1 (salvihispin): clear crystal；UV(MeOH)
λmax(logε)206(4.36),279(3.50)nm；IR(KBr)νmax 3432,2927,1754,1309,1045,732and
603cm-1；1H NMR and 13C NMR data see Table 2.12；ESIMS(positive)m/z 375[M+Na]+；
HRESIMS(positive)m/z377.0791[M+K]+(calcd for C20H18O5K,377.0786).
Compound 2 (salvifaricin): white powder；C20H20O5；1H NMR(600MHz,acetone-d6):δH6.01 (1H, dd, J=9.3,2.0, H-1), 6.31 (1H, m, H-2), 6.82 (1H, d, J=5.5, H-3), 2.04 (1H, m, H-
6a), 1.33 (1H, d, J=14.0, H-6b), 4.27 (1H, d, J=3.7, H-7), 1.95 (1H, m, H-8), 2.80 (1H, d, J
=5.6, H-10), 2.80 (1H, m H-11a), 1.97 (1H, m, H-11b), 5.28 (1H, t, J=7.8, H-12), 6.37 (1H,
Brs, H-14), 7.49 (1H, overlap, H-15), 7.49 (1H, overlap, H-16), 1.33 (3H, d, J=7.0, Me-
17), 4.04 (1H, d, J=8.0, H-19a), 4.93 (1H, d, J=8.0, H-19b), 5.31 (1H, s, H-20)；13CNMR
(150MHz,acetone-d6):δC 134.5(d,C-1),124.2(d,C-2),127.8(d,C-3),129.9(s,C-4),
59.0(s,C-5),40.0(t,C-6),84.9(d,C-7),40.1(d,C-8),39.0(s,C-9),49.5(d,C-10),39.0
(t,C-11),76.1(d,C-12),127.7(s,C-13),109.6(d,C-14),144.5(d,C-15),139.8(d,C-
16),15.1(q,C-17),169.6(s,C-18),81.1(t,C-19),110.6(d,C-20).Through with salvifaricin
(Savona,G.；Raffa,D.；Bruno,M.；Rodriguez,B.Phytochemistry 1983,22,784.)(Eguren,
L.；Fayos,J.；Perales,A.；Savona,G.；Rodriguez, B.Phytochemistry 1984,23,466)1H
With13C nuclear magnetic data compares, and is accredited as the same compound.
The hydrogen spectrum and carbon modal data of 1 compound 1 of table
a Measured at a600MHz,b150MHz.
Embodiment 2:
Activity of the compound 1 and 2 in terms of diabetes and Metabolic Syndrome:
Experimental animal and grouping:
C57BL/KsJdb/db mouse (db/db mouse) is congenital II caused by by plain (Leptin) acceptor gene defect
Patients with type Ⅰ DM mouse reacts because it lacks full sense substance (leptin), is mainly shown as overfeeding, fat, with hyperglycemia, high pancreas
The Abnormality of Glycolipid Metabolism features such as island element mass formed by blood stasis, insulin resistance, hyperlipidemia, with human type II diabetes' clinical symptoms extremely phase
Seemingly.
Tested C57BL/KsJdb/db mouse is 6 week old male mices, and SPF grades, weight 20-24g, raising is purchased from China
Shanghai institute of materia medica, the academy of sciences.Rearing conditions are according to SPF grades of minimal standards raising operating instruction raisings, except necessary fasting time
Outside, free diet drinking-water, feed is conventional feed.
Experimental material:
The beige crystals of compound 1 and 2, it is first as solvent (VPEG400:V water=3:7) using the mixed liquor of PEG400 and water
PEG400 is added after being ground into fine powdered with mortar by several times to be ground to uniformly, then by several times be added suitable quantity of water continue to be ground to it is uniform
Shape.Experiment principle presses standard practice instructions.
Experimental method:
1) animal packet: group 1 is model control group, and group 2 is melbine administration group, and group 3 is 1 administration group of compound, group 4
Position 2 administration group of compound, group 5 are brood normal mice, and experimental animal grouping and dosage are as shown in table 2.
The grouping of 2 experimental animal of table
| Group | Experimental animal | Size of animal (n) | Test medicine | Tested material dosage (mg/kg) |
| 1 | db/db | 10 | 5 ‰ CMC-Na (solvent) | 0 |
| 2 | db/db | 10 | Melbine | 200 |
| 3 | db/db | 10 | 1 | 100 |
| 4 | db/db | 10 | 2 | 100 |
| 5 | C57 | 10 | 5 ‰ CMC-Na (solvent) | 0 |
2) administration and detection
Fasting blood-glucose detection: db/db mouse routine monitoring, adaptable fed after a week, give before drug 1 day (P-1) again
Secondary progress blood glucose, weight detection；Tested material presses above table concentration dissolved dilution, stomach-filling (PO) administration, and the administration same day is denoted as P0；
It is administered between daily 14:00p.m.-16:00p.m., continues 34 days, during which track and record weight；The consumption of measurement in every 3 days food after administration
Amount, every 7 days measurement empty stomach 6h blood glucose, periodic logging consume appetite；
Grape sugar is resistant to (OGTT) detection: first 1 day of experiment, after each group mouse fasting 12h detects blood glucose, with 0.25g/kg stomach-filling
Glucose is given, in 15min, 30min, 60min, five time point difference tail veins of 90min, 120min measure each group blood glucose,
Draw area under OGTT curve, calculated curve；
Insulin resistant (ITT) detection: 0.8IU/kg insulin is injected intraperitoneally in experimental day each group mouse fasting,
Tetra- time point difference tail veins of 30min, 60min, 90min, 120min measure each group blood glucose, draw ITT curve, calculated curve
Lower area；
The detection of the indexs of correlation such as serum levels of triglyceride, cholesterol levels: serum is taken to measure index of correlation after experiment.
Animal performance, weight, water intake of ingesting during conventional record experiment carries out.
3) statistical method
All statistics are carried out using PASW Statistics 18 (SPSS18.0).It is vertical sit with blood glucose value or weight
Mark, administration group are respectively that abscissa takes statistics figure.Using the time as abscissa, blood sugar concentration is that ordinate sits OGTT, ITT curve.
Using Serum Indexes as ordinate, test medicine is that abscissa takes statistics figure.Statistical data is indicated using average ± standard deviation, is adopted
With one-way analysis of variance (One Way ANOVA), p < 0.05 thinks there is significant difference.
Experimental result:
1) influence of the compounds of this invention 1 and 2 pair db/db diabetic mice weight:
For db/db mouse in first 1 day record weight is administered, weighing in every 3 days is primary, compares each group mouse weight.The body of mouse
Weight change curve is as shown in Figure 3.
Experimental result shows, administration group mouse weight is without being decreased obviously compared with the control group.
2) influence of the compounds of this invention 1 and 2 pair db/db diabetic mice fasting blood-glucose:
Db/db mouse is after first 1 day detection fasting blood-glucose of administration, the successive administration of compound 1 and 2, every 7 days detection empty stomach 6h
Blood glucose, periodic logging consume appetite；The fasting plasma glucose result of mouse is as shown in Figure 4.
Experimental result shows that compound 1 and 2 is substantially reduced db/db as positive control drug melbine upon administration
Mouse fasting blood-glucose content, faster compared with melbine, padding improves obvious for effect；
3) influence of the compounds of this invention 1 and 2 pair db/db diabetic mice oral glucose tolerance (OGTT):
After each group mouse fasting 12h detects blood glucose, glucose is given with 0.25g/kg stomach-filling, in 15min, 30min,
60min, 90min, 120min five time points difference tail veins measure each group blood glucose, draw OGTT curve, below calculated curve
Product (Area under curve, AUC).The oral glucose tolerance curve and area under the curve statistical result of mouse are as shown in Figure 5.
4) influence of the compounds of this invention 1 and 2 pair db/db diabetic mice insulin tolerance (ITT):
After each group mouse fasting 6h detects blood glucose, 0.8IU/kg insulin is injected intraperitoneally, in 30min, 60min, 90min,
Tetra- time point difference tail veins of 120min measure each group blood glucose.The ITT curve and area under the curve statistical data of each group mouse
As shown in Figure 6.
Experimental result shows that compound 1 and 2 significantly improves insulin tolerance (* * p < 0.01vs of db/db mouse
Control, * * * p < 0.001vs Control), increase insulin sensitivity.
5) influence of the compounds of this invention 1 and 2 pair db/db diabetic mice serum indices:
Be administered the 34th day, to each group mice serum carried out triglyceride levels (TG), glucose content (Glucose),
The related assays of glutamic-oxalacetic transaminease activity (AST), gpt activity (ALT).Each group mice serum index of correlation measurement knot
Fruit is as shown in Figure 7.
Experimental result shows that the administration group of compound 1 and 2 mice serum glucose content significantly reduces compared with the control group
(p < 0.001 * * *), while reducing serum triglyceride level reduction (p < 0.001 * * *)；To glutamic-oxalacetic transaminease activity and paddy third
Transaminase activity has certain increase trend, but unobvious with control group statistical difference, illustrates no hepatotoxicity.
Embodiment 3
The preparation of tablet:
Compound 1 and 2 is first made as described in Example 1, and utilizes organic acid (tartaric acid, lemon rubber acid, formic acid, second
Diacid etc.) or inorganic acid (hydrochloric acid, sulfuric acid, phosphoric acid etc.) made of salt, in its with excipient weight than the ratio for 1:5-1:10
Excipient, pelletizing press sheet is added.
Embodiment 4
The preparation of oral liquid formulations:
Compound 1 and 2 is first made as described in Example 1, and utilizes organic acid (tartaric acid, lemon rubber acid, formic acid, second
Diacid etc.) or inorganic acid (hydrochloric acid, sulfuric acid, phosphoric acid etc.) made of salt, routinely oral solution is made in oral solution preparation method.
Embodiment 5
The preparation of capsule, granule or electuary:
Compound 1 and 2 is first made as described in Example 1, and utilizes organic acid (tartaric acid, lemon rubber acid, formic acid, second
Diacid etc.) or inorganic acid (hydrochloric acid, sulfuric acid, phosphoric acid etc.) made of salt, be added than the ratio for 5:1 in it with excipient weight and assigned
Capsule or granule or electuary is made in shape agent.
Claims (6)
1. Crow alkane type diterpenoid 1 shown in following structural formula (1),
2. Crow alkane type diterpenoid 1 or 2 shown in following structural formula treats or prevents type-2 diabetes mellitus and high in fat in preparation
Application in the drug of mass formed by blood stasis,
3. Crow alkane type diterpenoid 1 or 2 shown in structural formula treats or prevents type-2 diabetes mellitus in preparation in claim 2
With the application in the health food of hyperlipidemia.
4. the preparation method of Crow alkane type diterpenoid 1 or 2 shown in structural formula in claim 2, it is characterised in that the party
Method includes the following steps: that taking the aerial part of chia to shine dry doubling crushes, and is extracted three times, merging mentions three times with acetone cold soaking
Liquid is taken, is concentrated under reduced pressure, obtains total medicinal extract, for the medicinal extract through silica gel column chromatography, petroleum ether/acetone is 9:1,8:2,7:3,6:4, warp
TLC inspection is known, and is merged according to principal spot, and 5 components are obtained, and the inverted medium pressure liquid chromatography MPLC MCI of the 5th component is carried out
Separation is eluted with ethyl alcohol water system gradient 70:30,75:25,80:20,85:15,90:10 and 95:5, through combining data detection at 5 Asias
Component Fr.5.1~F.5.5；Component Fr.5.1 is placed a large amount of crystal of precipitation and obtains the 1, the 4th component of compound through silica gel column layer
Analysis, petroleum ether/chloroform/ethyl acetate are 4:4:1, obtain compound 2.
5. pharmaceutical composition, wherein containing Crow alkane type diterpenoid 1 shown in structural formula in claim 1 and pharmaceutically may be used
The carrier of receiving.
6. pharmaceutical composition, wherein containing Crow alkane type diterpenoid 1 or 2 and pharmacy shown in structural formula in claim 2
Upper acceptable carrier.
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Non-Patent Citations (2)
| Title |
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| DEAN J. TANTILLO: "How an Enzyme Might Accelerate an Intramolecular Diels-Alder Reaction:Theozymes for the Formation of Salvileucalin B", 《ORGANIC LETTERS》 * |
| YIQIANG LI，等: "Isolation and Chemical Modification of Clerodane Diterpenoids from Salvia Species as Potential Agonists at the k-Opioid Receptor", 《CHEMISTRY & BIODIVERSITY》 * |
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