CN101367861A - 2-hydroxyl-3-deoxidized pentacyclic triterpenoid and derivant, preparation method and uses thereof - Google Patents

2-hydroxyl-3-deoxidized pentacyclic triterpenoid and derivant, preparation method and uses thereof Download PDF

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CN101367861A
CN101367861A CNA2007100261092A CN200710026109A CN101367861A CN 101367861 A CN101367861 A CN 101367861A CN A2007100261092 A CNA2007100261092 A CN A2007100261092A CN 200710026109 A CN200710026109 A CN 200710026109A CN 101367861 A CN101367861 A CN 101367861A
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deoxidation
acid
hydroxyl
deoxidized
oleanolic acid
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孙宏斌
郝佳
张璞
柳军
张陆勇
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China Pharmaceutical University
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China Pharmaceutical University
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Abstract

The present invention relates to the field of medicines, in particular to a pentacyclic triterpene compound with a series of formula (I) or (II) and a preparation method and applications in the preparation of medicines used to prevent and treat diabetes, angiocardiopathy, cerebrovascular disease and tumors thereof. The definition of R1-8 can be seen in the description.

Description

2-hydroxyl-3-deoxidized pentacyclic triterpenoid and derivative thereof, Preparation Method And The Use
Technical field
The present invention relates to pharmaceutical field, be specifically related to a series of 2-hydroxyls-3-deoxidized pentacyclic triterpenoid and derivative thereof, the invention also discloses the preparation method and the medicinal use thereof of above-claimed cpd, especially in the application for preparing aspects such as antidiabetic medicine, anti-cerebral ischemia drugs, anti-cardiovascular disease, blood lipid-lowering medicine, anticholesteremic agent, slimming medicine, Antiatherosclerosis medicine, antitumor drug, inverase and Antihepatitis medicament.
Background technology
The distribution of pentacyclic triterpenoid in vegitabilia is very extensive, be the main effective constituent of many herbal medicine commonly used (as Radix Glycyrrhizae, skunk bush and Glossy Privet Fruit etc.), have protect the liver, anti-inflammatory, wide biological activity (Nat.Prod.Rep. such as antiviral, anti-oxidant, antitumor and hypoglycemic, 2006,23,394-411; Botanical Studies, 2006,47,339-368).
Aspect hypoglycemic, Liu Zhanbiao etc. have reported that Oleanolic Acid has significant blood sugar decreasing effect (Chinese Pharmaceutical Journal to tetraoxypyrimidine inductive hyperglycemic rat, 1994,29,725-726), the research of Miao Detian etc. further affirmed Oleanolic Acid hypoglycemic activity (People's Armed Police medical college journal 1998,7,148-150).The Korea S scholar reported recently ursolic acid, corosolic acid represent the novel PTP1B inhibitor of a class (Planta Med.2006,72,261-263), and PTP1B is considered to a target spot with treatment diabetes B of very big potentiality.Contriver Chinese patent application CN 1682740A in advance discloses pentacyclic triterpenoid and has had the effect that suppresses glycogen phosphorylase, thereby can be used for hypoglycemic, ischemia resisting cardiovascular and cerebrovascular diseases, antitumor and reducing blood-fat etc.
Aspect resisting cardiovascular disease, Fujimoto etc. have reported some natural pentacyclic triterpene compounds energy high degree of specificity ground antagonism human endothelin A receptors, and the compound S-0139 that obtains through structural modification has better activity and bioavailability.S-0139 now entered II phase clinical study be used for the treatment of cardiovascular and cerebrovascular diseases (Current Opinion in InvestigationalDrugs, 2002,3,1051-1055).Somova etc. have reported the antihypertensive function (Phytomedicine of Oleanolic Acid; 2003; 10; 115-121); and further experimental verification Oleanolic Acid, ursolic acid, methyl maslinate and Uvaol etc. have cardiac stimulant and anti-heart disorder activity (Phytomedicine; 2004,11,121-129).Arjunolic acid is a kind of pentacyclic triterpene acid that is separated to from the A Jiang Canarium album, studies show that, arjunolic acid to Racemic isoproterenol inductive myocardial abnormality have significant Cardioprotective effect (Bio.Pharm.Bull.2003,26,41-46).Sudharsan etc. have reported the myocardial damage that Lupeol can anti-endoxan causes, the prompting Lupeol have cardioprotection (Human Exp.Tox., 2005,24,313-318).Guan Teng etc. have reported that Crategolic acid has the effect of significant ischemia resisting brain injury, the prompting Crategolic acid can be used as anti-cerebral ischemia drugs (Chinese clinical pharmacology and therapeutics, 2007,12,381-384).
Aspect the adjusting lipid metabolism, Lee etc. have reported that natural pentacyclic triterpene compound is novel ACAT inhibitor (Biol.Pharm.Bull.2006,29,382-384), and ACAT is decreasing cholesterol and antiatherogenic active drug target spot, points out this compounds can make reducing blood-fat and Antiatherosclerosis medicine.PCT patent application WO03011267 has reported that pentacyclic triterpene compounds such as Crategolic acid and ursolic acid can be used as diet pill.
Protecting the liver/anti-hepatitis aspect, Oleanolic Acid and Potenlini preparation have obtained widespread use clinically as Antihepatitis medicament.
At anti-tumor aspect, it is clinical that Betulinic acid enters the I phase in the U.S. as the melanoma medicine.It is clinical that a derivative-CDDO of Oleanolic Acid has entered the I phase as antitumour drug.Chinese patent application CN1650869 has reported the anticancer effect of Bayogenine.U.S. Patent application 6174876 has been reported the application of masticinic acid aspect the treatment cancer of the brain.
At anti-virus aspect, it is clinical that a derivative-PA-457 of Betulinic acid enters the II phase in the U.S. as inverase.Hispanic Carcia-Granados etc. also confirmed Crategolic acid as the hiv virus proteinase inhibitor the potential using value aspect the anti-AIDS (Spain Patent:ES 2140329,2000-2-16).Anti-SARS virus activity (Lancet, 2003,361, the 2045-2046 of report Potenlini such as Cinatl and derivative thereof; J.Med.Chem., 2005,48,1256-1258).Baltina etc. have reported that white birch acid and derivative thereof have resisiting influenza virus and simplexvirus activity (Bioorganic ﹠amp; Medicinal Chemistry Letters 2003,13,3549-3552).
Aspect anti-inflammatory; Banno etc. have reported corosolic acid, and the inductive inflammatory reaction has significant inhibitory effect to TPA (12-O-four decanoyl phorbol-13-acetic ester), and its anti-inflammatory action is better than antiphlogiston indomethacin (Biosci Biotech.Biochem, 2004; 68,85-90).Aggarwal etc. have reported that the anti-inflammatory action of ursolic acid may realize (Cancer Res.2003,63,4375) by suppressing nf kappa-B.
Summary of the invention
Mostly the pentacyclic triterpenoid of bibliographical information is 3-hydroxyl or 2 before this, 3-dihydroxyl pentacyclic triterpenoid and derivative thereof, the present invention discloses the regional isomer of 3-hydroxyl pentacyclic triterpenoid first: 2-hydroxyl-3-deoxidized pentacyclic triterpenoid and derivative thereof, its preparation method and medicinal use are in particular for treatment diabetes (particularly diabetes B) and complication thereof, ischemic cardiovascular (myocardial infarction particularly, stenocardia, irregular pulse, coronary heart disease etc.), cerebral ischemia disease (apoplexy particularly, cerebral infarction and ischemia nerve degenerative diseases etc.), metabolism syndrome, hyperlipidemia, atherosclerosis, inflammation, fat, hypertension, hepatitis, HIV infects, influenza, SARS virus infection and tumour etc.
New compound disclosed by the invention comprises the pentacyclic triterpenoid shown in general formula I and the general formula I I or its pharmacy acceptable salt or ester:
Figure A200710026109D00091
R wherein 1Independent hydrogen, the OR of representing 9, NHR 9, N (R 10) 2, SO 2NH 2, NHOR 9, NH 2NHR 9R 2Independent hydrogen, the OR of representing 9, NHR 9, N (R 10) 2, SO 2NH 2, NHOR 9, NH 2NHR 9Perhaps R 1With R 2Represent O or NOR together 9
R 3Represent hydrogen or methyl, R 4Represent hydrogen or methyl, and, R worked as 3When representing hydrogen, R 4Represent methylidene only; Work as R 3During represent methylidene, R 4Only represent hydrogen;
R 5Represent CH 3, CH 2OR 9, COOR 10, CONHR 9, CON (R 10) 2, NHR 9
R 6Independent hydrogen, the OR of representing 9, NHR 9, N (R 10) 2, SO 2NH 2, NHOR 9, NH 2NHR 9R 7Independent hydrogen, the OR of representing 9, NHR 9, N (R 10) 2, SO 2NH 2, NHOR 9, NH 2NHR 9Perhaps R 6With R 7Represent O or NOR together 9
R 8Represent CH 3, CH 2OR 9, COOR 10, CONHR 9, CON (R 10) 2, NHR 9
R 9Represent hydrogen or R 10, R 10CO, R 10SO 2
R 10Represent straight or branched alkane, alkene, alkynes, phenyl, benzyl, the naphthyl non-replacement or that X replaces of 1～10 carbon;
X represents H, F, Cl, Br, I, CN, NO 2, NH 2, CF 3, SH, OH, OCH 3, OC 2H 5, COOH, COOCH 3, COOC 2H 5, 1～10 carbon straight or branched alkane, alkene, alkynes, phenyl, benzyl, naphthyl.
Preferred compound is in the above-claimed cpd:
R wherein 1Independent hydrogen, the OR of representing 9R 2Independent hydrogen, the OR of representing 9Perhaps R 1With R 2Represent O or NOR together 9
R 3Represent hydrogen or methyl, R 4Represent hydrogen or methyl, and, R worked as 3When representing hydrogen, R 4Represent methylidene only; Work as R 3During represent methylidene, R 4Only represent hydrogen;
R 5Represent CH 3, CH 2OR 9, COOR 10
R 6Independent hydrogen, the OR of representing 9R 7Independent hydrogen, the OR of representing 9Perhaps R 6With R 7Represent O or NOR together 9
R 8Represent CH 3, CH 2OR 9, COOR 10
R 9Represent hydrogen or R 10, R 10CO;
R 10Represent straight or branched alkane, alkene, alkynes, phenyl, benzyl, the naphthyl non-replacement or that X replaces of 1～10 carbon;
X represents H, F, Cl, Br, I, CN, NO 2, NH 2, CF3, SH, OH, OCH 3, OC 2H 5, COOH, COOCH 3, COOC 2H 5, 1～10 carbon straight or branched alkane, alkene, alkynes, phenyl, benzyl, naphthyl.
More preferred compound is:
2-carbonyl-3-deoxidation Oleanolic Acid-28-benzyl ester
2-carbonyl-3-deoxidation ursolic acid-28-benzyl ester
2-carbonyl-3-deoxidation Oleanolic Acid
2-carbonyl-3-deoxidation ursolic acid
2-oximido-3-deoxidation Oleanolic Acid-28-benzyl ester
2-oximido-3-deoxidation ursolic acid-28-benzyl ester
2-oximido-3-deoxidation Oleanolic Acid
2-oximido-3-deoxidation ursolic acid
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-benzyl ester
2-(β)-hydroxyl-3-deoxidized ursolic acid-28-benzyl ester
2-(α)-hydroxyl-3-deoxidized oleanolic acid-28-benzyl ester
2-(α)-hydroxyl-3-deoxidized ursolic acid-28-benzyl ester
2-(β)-hydroxyl-3-deoxidized Oleanolic Acid
2-(β)-hydroxyl-3-deoxidized ursolic acid
2-(α)-hydroxyl-3-deoxidized oleanolic acid
2-(α)-hydroxyl-3-deoxidized ursolic acid
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-methyl esters
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-ethyl ester
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-propyl ester
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-butyl ester
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-allyl ester
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-(2-bromine ethyl ester)
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-(3-bromine propyl ester)
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-(4-bromine butyl ester)
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-ethyl acetate
2-(β)-acetoxy-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-propionyloxy-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-butyryl acyloxy-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-benzoyloxy-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-to tert.-butylbenzene methanoyl-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-O-succinyl-3-deoxidation oleanolic acid-28-benzyl ester
2-(β)-acetoxy-3-deoxidation-oleanolic acid
2-(β)-propionyloxy-3-deoxidation-oleanolic acid
2-(β)-butyryl acyloxy-3-deoxidation-oleanolic acid
2-(β)-benzoyloxy-3-deoxidation-oleanolic acid
2-(β)-to tert.-butylbenzene methanoyl-3-deoxidation-oleanolic acid
2-(β)-O-succinyl-3-deoxidation oleanolic acid
2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation oleanolic acid
2-(β)-O-(2 ', 2 '-dimethyl succinyl)-3-deoxidation oleanolic acid
1-alkene-2-hydroxyl-3-carbonyl-28-trityl ether trochol
2-(β)-hydroxyl-28-trityl ether trochol
2-carbonyl-3-deoxidation-28-trityl ether trochol
2-carbonyl-3-deoxidation-28-acetic ester trochol
2-carbonyl-3-deoxidation trochol
2-(β)-hydroxyl-3-deoxidized-28-trityl ether trochol
2-(α)-hydroxyl-3-deoxidized-28-trityl ether trochol
2-(β)-hydroxyl-3-deoxidized trochol
2-(α)-hydroxyl-3-deoxidized trochol
2-(β)-acetoxy-3-deoxidation-28-trityl ether trochol
2-(β)-butyryl acyloxy-3-deoxidation-28-trityl ether trochol
2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation-28-trityl ether trochol
2-(β)-O-(2 ', 2 '-dimethyl succinyl)-3-deoxidation-28-trityl ether trochol
2-(β)-acetoxy-3-deoxidation trochol
2-(β)-propionyloxy-3-deoxidation trochol
2-(β)-butyryl acyloxy-3-deoxidation trochol
2-(β)-benzoyloxy-3-deoxidation trochol
2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation trochol
2-(β)-O-(2 ', 2 '-dimethyl succinyl)-3-deoxidation trochol
2-carbonyl-3-deoxidation white birch acid
2-(β)-hydroxyl-3-deoxidized white birch acid
Pentacyclic triterpenoid shown in general formula I and the general formula I I all is new compounds, and these new compounds can prepare with method as follows, as:
The preparation of 2-carbonyl-3-deoxidation pentacyclic triterpene compound:
Figure A200710026109D00121
In the following formula, R 3, R 4, R 5And R 8Described as defined above.(2 β, 3 β)-2 in the following formula, but the preparation reference literature method of 3-dihydroxyl pentacyclic triterpene compound (Collection of Czechoslovak Chemical Communications, 1989,54,1036-42) carry out.Under base catalysis, (2 β, 3 β)-2,3-dihydroxyl pentacyclic triterpene compound and Tosyl chloride or benzene sulfonyl chloride reaction obtain 2-carbonyl-3-deoxidation pentacyclic triterpene compound.The alkali that is adopted comprises pyridine, triethylamine, salt of wormwood, yellow soda ash, sodium bicarbonate, saleratus, sodium hydroxide and potassium hydroxide, preferentially adopts pyridine.The solvent that is adopted comprises pyridine, methylene dichloride, 1,2-ethylene dichloride, chloroform, toluene, N, dinethylformamide (DMF), N, N-N,N-DIMETHYLACETAMIDE (DMA), acetonitrile, tetrahydrofuran (THF) and dioxane, perhaps with the optional mixed solvent of forming of these solvents, preferential pyridine, 1,2-ethylene dichloride, toluene, N, dinethylformamide or the tetrahydrofuran (THF) of adopting.Temperature of reaction can be controlled in 0 degree to 150 degree, preferentially adopts room temperature to 80 degree as temperature of reaction.
The preparation of 2-oximido-3-deoxidation pentacyclic triterpene compound:
Figure A200710026109D00131
In the following formula, R 3, R 4, R 5And R 8Described as defined above.2-carbonyl in the following formula-3-deoxidation pentacyclic triterpene compound and oxammonium hydrochloride react under base catalysis, generate 2-oximido-3-deoxidation pentacyclic triterpene compound.The alkali that is adopted comprises pyridine, triethylamine, salt of wormwood, yellow soda ash, sodium bicarbonate, saleratus, sodium hydroxide and potassium hydroxide, preferentially adopts pyridine.The solvent that is adopted comprises pyridine, methylene dichloride, 1,2-ethylene dichloride, chloroform, toluene, N, dinethylformamide (DMF), N, N-N,N-DIMETHYLACETAMIDE (DMA), acetonitrile, tetrahydrofuran (THF) and dioxane, perhaps with the optional mixed solvent of forming of these solvents, preferential pyridine, 1,2-ethylene dichloride, toluene, N, dinethylformamide or the tetrahydrofuran (THF) of adopting.Temperature of reaction can be controlled in 0 degree to 150 degree, preferentially adopts room temperature to 80 degree as temperature of reaction.
The preparation of the hydroxyl-3-deoxidized pentacyclic triterpene compound of 2-:
Figure A200710026109D00132
In the following formula, R 3, R 4, R 5And R 8Described as defined above.2-carbonyl in the following formula-3-deoxidation pentacyclic triterpene compound generates the hydroxyl-3-deoxidized pentacyclic triterpene compound of 2-under the effect of reductive agent.The reductive agent that is adopted is selected from sodium borohydride, POTASSIUM BOROHYDRIDE, Virahol/aluminum isopropylate, borine/tetrahydrofuran (THF) and borine/dimethyl sulphide, preferentially adopts sodium borohydride (potassium).The solvent that is adopted is selected from tetrahydrofuran (THF), ethanol, methyl alcohol, ether, t-butyl methyl ether, ethyl acetate, ethyl formate, methyl acetate ,The mixture of dioxane or above-mentioned solvent preferentially adopts tetrahydrofuran (THF)/ethanol as reaction solvent.Temperature of reaction can be controlled in zero degree to 60 degree, preferentially adopt zero degree to room temperature as temperature of reaction.
The preparation of 2-O-acyl group-3-deoxidation pentacyclic triterpene compound:
Figure A200710026109D00141
In the following formula, R 3, R 4, R 5, R 8And R 10Described as defined above.According to the hydroxy esterification method of routine, the hydroxyl-3-deoxidized pentacyclic triterpene compound of the 2-in the following formula and various acyl chlorides, acid anhydrides or carboxylic acid reaction obtain 2-O-acyl group-3-deoxidation pentacyclic triterpene compound.
The preparation of 3-deoxidation pentacyclic triterpene-28-ester cpds:
Figure A200710026109D00142
In the following formula, R 1, R 2, R 3, R 4, R 6, R 7And R 10Described as defined above.According to the carboxyalkyl esterification process of routine, the 3-deoxidation pentacyclic triterpene in the following formula-28-acid and various halogenated alkane reactions obtain 3-deoxidation pentacyclic triterpene-28-ester cpds.
Be part pharmacology test and result below:
One, 2-hydroxyl-3-deoxidized pentacyclic triterpenoid and derivative thereof are to the experiment of glycogen phosphorylase inhibitory activity
The preparation of reagent: the 1) preparation of colour developing liquid: weighing ammonium molybdate 5g, be dissolved among the 500ml 1M HCl, stir with agitator, to all dissolving the back, continue to be stirred to whole dissolvings, and use the masking foil lucifuge adding Victoria Green WPB 190mg; 2) preparation of damping fluid: 1. precision weighing Hepes 0.5958g is dissolved in 5ml H 2Among the O, transfer PH to 7.2, be mixed with the Hepes that final concentration is 0.5M with 10M NaOH; 2. precision weighing KCl 0.3728g is dissolved in 5ml H 2Among the O, be mixed with the KCl that final concentration is 1M; 3. precision weighing MgCl 20.0255g, be dissolved in 1ml H 2Among the O, be mixed with the MgCl that final concentration is 125mM 24. precision weighing EGTA 0.0476g is dissolved in 5ml H 2Among the O, transfer PH to 7.0, be mixed with the EGTA that final concentration is 25mM with 10M NaOH; 5. precision weighing G-1-P 0.0152g is dissolved in 10ml H 2Among the O, be mixed with the G-1-P that final concentration is 5mM; 6. precision weighing glycogen 10mg is dissolved in 1ml H 2Among the O, be mixed with the glycogen that final concentration is 10mg/ml; 3) preparation of positive drug caffeine solution: caffeine is dissolved in 10ml H 2The solution of O preparation 0.5,5,50 and 500 μ M; 4) preparation GPa solution: the GPa that gets 1 μ l joins in the 100 μ l reaction systems, and final concentration is 250ng/100 μ l; 5) preparation of compound solution to be tested: compound to be tested is dissolved in DMSO, and to be mixed with concentration be 10mM solution, gets an amount of compound solution and join in the reaction system to different final concentrations.
Measure the active amount effect curve of rabbit muscle glycogen Starch phosphorylase:, measure its amount effect curve by the OD value under 655nm behind the GPa adding colour developing liquid that reads different concns.Can select the amount of GPa by amount effect curve is 250ng.
Experimental procedure: 1) design PC (positive control), Blank (blank), positive drug (caffeine); 2) add reaction buffer52 μ l; 3) add test compounds to final concentration; 4) enzyme-added 1 μ l, final concentration is 250ng/100 μ l; 5) add colour developing liquid 150 μ l; 6) reacted 20 minutes under 20～25 degrees celsius; 7) colorimetric under wavelength 655nm condition; 8) reading and the calculating of inhibiting rate of data: inhibiting rate=[positive control-testing sample]/[positive control-blank].
Test result: table 1 has been listed the inhibition activity data of part pentacyclic triterpene compound to rabbit muscle glycogen Starch phosphorylase, and the result shows that most pentacyclic triterpene compounds have significant inhibition activity to glycogen phosphorylase.
Table 1,2-hydroxyl-3-deoxidized pentacyclic triterpenoid and derivative thereof are to the inhibition activity of rabbit muscle glycogen Starch phosphorylase
Figure A200710026109D00151
Figure A200710026109D00161
Figure A200710026109D00171
Figure A200710026109D00191
Figure A200710026109D00201
*Inhibiting rate when concentration is 20 μ M; *Non-activity when concentration is 20 μ M; * *Non-activity when concentration is 2000 μ M.
By above test as seen, 2-hydroxyl provided by the present invention-3-deoxidized pentacyclic triterpenoid and derivative thereof have the activity that suppresses glycogen phosphorylase, therefore can be used for the treatment of and the unusual relevant disease of Glycogen Metabolism, as diabetes, ischemic cardio cerebrovascular diseases and tumour etc.In addition, in view of pentacyclic triterpenoid has many target spots and biological activity characteristics widely, 2-hydroxyl provided by the present invention-3-deoxidized pentacyclic triterpenoid and derivative thereof also can be used for atherosclerosis, anti-inflammatory, fat-reducing, reducing blood-fat, metabolism syndrome, hypotensive, protect the liver/anti-hepatitis, anti-HIV infection, anti influenza and anti-SARS virus infection etc.
Embodiment
Embodiment 1
The preparation of 2-carbonyl-3-deoxidation Oleanolic Acid-28-benzyl ester
2-(β)-hydroxyl Oleanolic Acid-28-benzyl ester (2g) is dissolved in the 15mL pyridine, adding Tosyl chloride (2.03g) stirred 24 hours for about 50 ℃, stop heating, the cooling back slowly drips 1N hydrochloric acid and regulates PH ≈ 3 in reaction solution, extract with ethyl acetate 30mL * 4, add the saturated sodium bicarbonate solution washing, add the saturated common salt water washing at last, get ethyl acetate layer, anhydrous Na 2SO 4Drying, evaporate to dryness, rapid column chromatography (sherwood oil: ethyl acetate=50:1), get 2-carbonyl-3-deoxidation Oleanolic Acid-28-benzyl ester 1.3g, yield: 62.5％。 1H?NMR(300MHz，CDCl 3)δ?ppm：0.59(s，3H)，0.88(s，6H)，0.90(s，3H)，0.92(s，3H)，1.05(s，3H)，1.16(s，3H)，2.92(dd，J＝4.0Hz，14.1Hz，1H)，5.02-5.12(m，2H)，5.23(t，J＝3.2Hz，1H)，7.26-7.36(m，5H)；13CNMR(300MHz，CDCl 3)δ?ppm：16.4，16.6，19.1，23.1，23.3，23.6，25.8，27.6，30.7，32.3，32.4，33.1，33.5，33.9，39.2，39.8，41.4，41.9，42.8，45.9，46.8，47.3，55.6，55.7，56.4，66.0，122.1，127.9，128.0，128.4，136.4，143.8，177.3，211.8；ESI-MS?m/z：583.2[M+K] +.
Embodiment 2
The preparation of 2-carbonyl-3-deoxidation ursolic acid-28-benzyl ester
With 2-(β)-hydroxyl ursolic acid-28-benzyl ester is raw material, makes 2-carbonyl 3-deoxidation ursolic acid-28-benzyl ester with reference to the method for embodiment 1. 1H?NMR(300MHz，CDC] 3)δ?ppm：0.61(s，3H)，0.86(s，3H)，0.88(s，3H)，0.89(s，3H)，0.97(s，3H)，1.06(s，3H)，1.11(s，3H)，2.34(d，J＝2.1Hz，1H)，4.97(d，J＝12.4Hz，1H)，5.10(d，J＝12.4Hz，1H)，5.23(brs，1H)，7.28-7.35(m，5H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：16.5，16.7，17.0，19.0，21.1，23.2，23.3，23.5，24.2，28.0，30.6，32.7，33.5，36.6，38.8，39.1，39.1，40.0，42.2，42.8，47.1，48.1，52.9，55.5，55.8，56.3，66.0，125.2，128.0，128.2，128.4，136.3，138.2，177.1，211.8；ESI-MS?m/z：545.4[M+H] +
Embodiment 3
The preparation of 2-carbonyl-3-deoxidation Oleanolic Acid
In 2-carbonyl-3-deoxidation Oleanolic Acid-28-benzyl ester (1.0g), add the 30mL tetrahydrofuran (THF), add 10%Pd/C (0.1g), the room temperature normal pressure hydrogenation spends the night, after raw material reaction is complete,, remove by filter Pd/C with tetrahydrofuran (THF) diluting reaction thing, filtrate gets powdery solid after boiling off solvent, add the color that an amount of normal hexane will adhere on a small quantity and remove, after the filtration white powder 3-isomery Oleanolic Acid 0.8g, yield: 95.9%. 1H?NMR(300MHz，C 5D 5N)δ?ppm：0.82(s，3H)，0.86(s，3H)，0.96(s，3H)，1.01(s，3H)，1.25(brs，6H)，1.29(s，3H)，3.30(d，J＝12.6Hz，1H)，5.46(brs，1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：14.3，16.5，17.0，19.3，22.8，22.9，23.4，23.7，23.8，26.1，28.3，29.6，29.9，30.0，31.0，32.1，32.8，33.1，33.2，33.3，34.3，39.1，39.6，40.1，42.0，42.3，43.0，46.5，46.7，47.5，55.4，55.6，56.5，122.1，144.9，180.1，210.3；ESI-MS?m/z：453.3[M-H] -.
Embodiment 4
The preparation of 2-carbonyl-3-deoxidation ursolic acid
With 2-carbonyl-3-deoxidation ursolic acid-28-benzyl ester is raw material, makes 2-carbonyl-3-deoxidation ursolic acid with reference to the method for embodiment 3. 1H?NMR(300MHz，C 5D 5N)δ?ppm：0.81(s，3H)，0.84(s，3H)，0.96(brs，9H)，1.22(brs，6H)，2.62(d，J＝10.68Hz，1H)，5.44(brs，1H)； 13C?NMR(300MHz，C 5D 5N)δ?ppm：16.7，17.1，17.5，19.3，21.4，23.4，23.6，23.9，24.9，28.7，31.1，33.1，33.3，37.4，39.0，39.4，39.6，40.4，42.7，42.9，47.4，48.1，53.6，55.5，55.9，56.5，125.2，139.4，179.8，210.4；ESI-MS?m/z：453.5[M-H] -.
Embodiment 5
The preparation of 2-oximido-3-deoxidation Oleanolic Acid-28-benzyl ester
2-carbonyl-3-deoxidation oleanolic acid-28-benzyl ester (0.1g) is dissolved in the 0.6mL pyridine, adds oxammonium hydrochloride (0.025g) stirring at room 3 hours.In reaction solution, slowly drip 1N hydrochloric acid adjusting PH ≈ 3, extract, add the saturated sodium bicarbonate solution washing, add the saturated common salt water washing at last, get ethyl acetate layer, anhydrous Na with ethyl acetate 10mL * 4 2SO 4Drying, evaporate to dryness, rapid column chromatography (sherwood oil: ethyl acetate=6:1), get 2-oximido-3-deoxidation Oleanolic Acid-28-benzyl ester 0.095g, yield 93.1%. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.59(s，6H)，0.83(s，3H)，0.84(s，6H)，0.86(s，3H)，0.90(s，6H)，0.92(s，6H)，1.00(s，3H)，1.03(s，3H)，1.15(s，6H)，2.92(dd，J＝4.1Hz，13.4Hz，2H)，3.14(d，J＝13.6Hz，1H)，3.29(d，J＝12.7Hz，1H)，5.01-5.13(m，4H)，5.30(brs，1H)，5.31(brs，1H)，7.28-7.35(m，10H)； 13CNMR(300MHz，CDCl 3)δ?ppm：15.5，15.9，16.6，16.7，22.3，22.8，23.1，23.4，23.5，23.6，25.8，27.6，30.7，32.3，32.4，32.5，32.8，33.1，33.9，36.8，38.7，39.4，39.6，39.7，40.7，40.8，41.4，41.8，45.9，46.2，46.8，47.0，47.2，56.3，56.4，65.9，66.0，122.3，127.9，128.0，128.4，136.4，143.6，143.7，159.4，159.5，177.3，177.4；ESI-MSm/z：560.4[M+H] +.
Embodiment 6
The preparation of 2-oximido-3-deoxidation ursolic acid-28-benzyl ester
With 2-carbonyl-3-deoxidation ursolic acid-28-benzyl ester is raw material, makes 2-oximido-3-deoxidation ursolic acid-28-benzyl ester with reference to the method for embodiment 5. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.63(s，6H)，0.81(s，3H)，0.83(s，3H)，0.85(s，6H)，0.86(s，6H)，0.95(s，6H)，1.01(s，3H)，1.04(s，3H)，1.10(s，6H)，3.15(dd，J＝1.9Hz，13.5Hz，1H)，3.32(d，J＝13.0Hz，1H)，4.95-5.14(m，4H)，5.25(m，2H)，7.25-7.36(m，10H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：15.6，16.1，16.7，16.8，16.9，18.7，18.8，21.1，22.3，22.9，23.3，23.4，23.5，24.3，28.0，30.7，32.7，32.8，32.8，32.9，36.6，36.9，37.0，38.8，39.0，39.1，39.5，39.9，40.0，40.8，41.0，42.1，42.2，46.1，46.6，47.0，47.1，48.1，52.9，56.2，56.3，66.0，125.4，127.9，128.2，128.4，136.3，138.1，138.2，160.3，177.1；ESI-MS?m/z：560.4[M+H] +.
Embodiment 7
The preparation of 2-oximido-3-deoxidation Oleanolic Acid
With 2-oximido-3-deoxidation Oleanolic Acid-28-benzyl ester is raw material, makes 2-oximido-3-deoxidation oleanolic acid with reference to the method for embodiment 3. 1H?NMR(300MHz，DMSO-d6)δ?ppm：0.71(s，3H)，0.72(s，3H)，0.76(s，6H)，0.81(s，3H)，0.88(brs，12H)，0.95(s，3H)，0.97(s，3H)，1.13(s，6H)，1.24(s，3H)，2.75(d，J＝10.4Hz，2H)，2.99(d，J＝13.0Hz，1H)，3.15(d，J＝12.3Hz，1H)，5.20(brs，2H)，10.15(s，1H)，10.17(s，1H)，12.05(brs，2H)； 13C?NMR(300MHz，CDCl3)δ?ppm：15.0，15.5，16.4，16.5，18.1，18.2，21.9，22.6，22.7，22.9，23.2，25.4，27.1，28.8，30.2，32.0，32.3，32.4，32.7，33.2，35.9，36.0，37.8，38.7，38.8，38.9，39.0，40.3，40.7，41.3，45.4，45.5，45.6，46.0，46.3，46.5，55.3，55.4，121.2，121.3，143.6，143.7，155.3，178.3；ESI-MS?m/z：468.3[M-H] -.
Embodiment 8
The preparation of 2-oximido-3-deoxidation ursolic acid
With 2-oximido-3-deoxidation ursolic acid-28-benzyl ester is raw material, makes 2-oximido-3-deoxidation ursolic acid with reference to the method for embodiment 3. 1H?NMR(300MHz，DMSO-d6)δ?ppm：0.75(s，12H)，0.82(s，12H)，0.92(s，6H)，0.95(s，3H)，0.96(s，3H)，1.08(s，6H)，2.99(d，J＝12.0Hz，1H)，3.17(d，J＝12.3Hz，1H)，5.15(brs，2H)，10.13(brs，2H)，11.93(brs，2H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：15.4，15.8，16.6，16.7，17.1，18.3，18.4，21.1，22.2，22.8，22.9，23.0，23.3，23.9，27.6，30.3，32.4，32.5，32.6，36.1，36.4，38.1，38.6，38.9，39.0，39.1，39.5，40.1，40.3，40.5，41.8，45.8，46.1，46.4，46.6，46.9，52.5，55.5，55.6，124.5，138.2，138.3，155.5，178.2；ESI-MS?m/z：470.4[M+H] +.
Embodiment 9
The preparation of the hydroxyl-3-deoxidized oleanolic acid of 2--28-benzyl ester
2-carbonyl-3-deoxidation oleanolic acid-28-benzyl ester (0.12g) is dissolved in the 5mL tetrahydrofuran (THF), adds 1ml ethanol, and ice bath is cooled to 0 ℃, adds sodium borohydride (0.012g), stirring at room 6 hours.In reaction solution, slowly drip 1N hydrochloric acid adjusting PH ≈ 3, extract, add the saturated sodium bicarbonate solution washing, add the saturated common salt water washing at last, get ethyl acetate layer, anhydrous Na with ethyl acetate 15mL * 4 2SO 4Drying, evaporate to dryness, rapid column chromatography (sherwood oil: ethyl acetate=25:1), get 2-(β)-hydroxyl-3-deoxidized Oleanolic Acid-28-benzyl ester 0.106g, yield 88%. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.63(s，3H)，0.86(s，3H)，0.93(s，6H)，1.01(s，3H)，1.13(s，3H)，1.16(s，3H)，2.92(d，J＝10.9Hz，1H)，4.08(brs，1H)，5.06-5.12(m，2H)，5.32(brs，1H)，7.26-7.34(m，5H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：16.8，18.5，19.0，23.1，23.4，23.6，24.6，25.9，27.5，29.7，30.7，32.4，32.5，32.6，33.1，33.9，37.8，39.6，41.5，41.9，45.9，46.6，46.8，47.2，48.0，53.5，65.9，67.6，122.8，127.9，128.0，128.4，136.5，143.7，177.4；ESI-MS?m/z：569.2[M+Na] +.
Obtain 2-(α)-hydroxyl-3-deoxidized Oleanolic Acid-28-benzyl ester 0.006g simultaneously, yield 5%. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.61(s，3H)，0.85(s，3H)，0.90(s，6H)，0.92(s，3H)，0.93(s，3H)，1.13(s，3H)，2.92(dd，J＝4.1Hz，13.7Hz，1H)，3.84-3.92(m，1H)，5.02-5.12(m，2H)，5.32(t，J＝3.2Hz，1H)，7.26-7.35(m，5H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：16.4，17.0，18.4，22.6，23.1，23.5，23.7，25.9，27.6，29.7，30.7，32.4，32.7，33.1，33.5，33.9，34.9，39.0，39.5，41.4，41.8，45.9，46.8，49.5，51.2，55.7，65.1，65.9，122.5，127.9，128.0，128.4，136.5，143.7，177.4；ESI-MS?m/z：569.2[M+Na] +.
Embodiment 10
The preparation of the hydroxyl-3-deoxidized ursolic acid of 2--28-benzyl ester
With 2-carbonyl-3-deoxidation ursolic acid-28-benzyl ester is raw material, makes 2-(β)-hydroxyl-3-deoxidized ursolic acid-28-benzyl ester with reference to the method for embodiment 9. 1H?NMR(300MHz，CDCl 3)δ?ppm?0.65(s，3H)，0.85(s，3H)，0.93(s，3H)，0.94(s，3H)，1.01(s，3H)，1.07(s，3H)，2.27(d，J＝11.3Hz，1H)，4.06-4.10(m，1H)，4.97(d，J＝12.5Hz，1H)，5.10(d，J＝12.5Hz，1H)，5.26(t，J＝3.6Hz，1H)，7.28-7.36(m，5H)； 13C?NMR(300MHz，CDCl 3)δ?ppm16.9，17.0，18.7，19.0，23.4，23.6，24.3，24.7，27.9，29.6，29.7，30.7，32.7，32.9，33.1，36.7，37.8，38.9，39.1，39.9，42.3，46.6，47.6，48.1，48.2，53.1，53.5，66.0，67.6，126.0，127.9，128.2，128.4，136.4，138.1，177.2；ESI-MS?m/z：569.4[M+Na] +.
Obtain 2-(α)-hydroxyl-3-deoxidized ursolic acid-28-benzyl ester simultaneously. 1H?NMR(300MHz，CDCl 3)δ?ppm?0.65(s，3H)，0.86(s，3H)，0.87(s，3H)，0.94(brs，6H)，0.95(s，3H)，1.08(s，3H)，2.27(d，J＝11.6Hz，1H)，3.89(m，1H)，4.98(d，J＝12.5Hz，1H)，5.10(d，J＝12.5Hz，1H)，5.25(t，J＝3.6Hz，1H)，7.26-7.36(m，5H)； 13C?NMR(300MHz，CDCl 3)δ?ppm16.6，17.0，17.1，18.4，21.1，22.7，23.4，23.6，24.3，28.0，30.7，33.0，33.6，34.9，36.7，38.9，39.0，39.2，39.8，42.2，47.7，48.2，49.8，51.3，53.0，55.7，65.2，66.0，125.8，128.0，128.2，128.4，136.5，138.3，177.2；ESI-MS?m/z：569.4[M+Na] +.
Embodiment 11
The preparation of 2-(β)-hydroxyl-3-deoxidized Oleanolic Acid
With 2-(β)-hydroxyl-3-deoxidized Oleanolic Acid-28-benzyl ester is raw material, makes 2-(β)-hydroxyl-3-deoxidized Oleanolic Acid with reference to the method for embodiment 3. 1H?NMR(300MHz，C 5D 5N)δ?ppm：0.82(s，3H)，0.86(s，3H)，0.96(s，3H)，1.01(s，3H)，1.25(brs，6H)，1.29(s，3H)，3.29(dd，J＝4.2Hz，13.8Hz，1H)，4.33-4.36(m，1H)，5.50(t，J＝3.3Hz，1H)； 13C?NMR(300MHz，C 5D 5N)δ?ppm：23.8，23.9，24.7，26.2，28.3，31.0，33.0，33.2，33.3，33.8，34.3，38.1，40.1，42.1，42.4，46.5，46.7，47.4，47.6，48.5，54.8，66.9，122.8，144.8，180.1；ESI-MS?m/z：479.3[M+Na] +.
Embodiment 12
The preparation of 2-(β)-hydroxyl-3-deoxidized ursolic acid
With 2-(β)-hydroxyl-3-deoxidized ursolic acid-28-benzyl ester is raw material, makes 2-(β)-hydroxyl-3-deoxidized ursolic acid with reference to the method for embodiment 3. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.79(s，3H)，0.85(s，3H)，0.87(s，3H)，0.92(s，3H)，0.93(s，3H)，0.99(s，3H)，1.25(S，3H)，4.08(brs，1H)，5.28(brs，1H)； 13C?NMR(300MHz，C 5D 5N)δ?ppm：17.6，18.4，19.3，21.4，23.9，24.0，24.8，25.1，28.7，31.2，33.0，33.5，33.8，37.5，38.0，39.5，39.6，40.4，42.9，47.7，47.8，48.2，48.6，53.8，54.8，66.9，126.0，139.3；ESI-MS?m/z：455.3[M-H] -.
Embodiment 13
2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation oleanolic acid and
The preparation of 2-(β)-O-(2 ', 2 '-dimethyl succinyl)-3-deoxidation oleanolic acid
2-(β)-hydroxyl-3-deoxidized Oleanolic Acid-28-benzyl ester (0.15g) is dissolved in the pyridine (2ml), add 2,2-dimethyl succinic anhydride (0.11g) and DMAP (0.07g), 85 ℃ of stirrings, add 2N hydrochloric acid (15ml) neutralization after 15 hours, with ethyl acetate extraction three times, organic layer is extremely neutral with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, anhydrous sodium sulfate drying, filter, concentrate, rapid column chromatography (petrol ether/ethyl acetate=3/1), get 2-(β)-(3-carboxyl-3-methyl isophthalic acid-butyryl acyloxy)-3-deoxidation oleanolic acid-28-benzyl ester and 2-(β)-(3-carboxyl-2,2-dimethyl-1-propionyloxy)-3-deoxidation oleanolic acid-28-benzyl ester mixture colorless solid 140mg, yield 77.0%.With gained mixture (0.13g), be dissolved among the DMF (1.5ml), add salt of wormwood (0.04g, 0.28mmol, 1.5eq), the dropping Benzyl Chloride (0.026ml, 0.23mmol, 1.2eq), stirring at room, add entry (10ml) after 5 hours, use ethyl acetate extraction three times, organic layer is extremely neutral with the saturated common salt water washing, anhydrous sodium sulfate drying, filter, concentrate rapid column chromatography (petrol ether/ethyl acetate=60/1), get 2-(β)-(4-benzyl ester-3,3-dimethyl succinic acid ester)-and 3-deoxidation oleanolic acid-28-benzyl ester, colorless solid 70mg, yield 48.2%.Obtain 2-(β)-(4-benzyl ester-2,2-dimethyl succinic acid ester)-3-deoxidation oleanolic acid-28-benzyl ester simultaneously, colorless oil 20mg, yield 13.8%.
With 2-(β)-(4-benzyl ester-3,3-dimethyl succinic acid ester)-3-deoxidation oleanolic acid-28-benzyl ester is raw material, makes 2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation oleanolic acid with reference to the method for embodiment 3. 1H?NMR(300MHz，C 5D 5N)δppm：0.87(s，3H)，0.96(s，3H)，0.99(s，3H)，1.00(s，3H)，1.02(s，3H)，1.17(s，3H)，1.24(s，3H)，1.53(s，6H)，2.86(d，J＝1.2Hz，2H)，3.29(dd，J＝3.3Hz，13.8Hz，1H)，5.27(m，1H)，5.47(brs，1H)； 13C?NMR(300MHz，C 5D 5N)δ?ppm：17.3，17.4，18.9，23.6，23.7，24.0，25.9，26.0，26.1，28.2，29.9，30.9，32.5，32.9，33.2，33.3，34.2，37.5，39.9，40.8，42.0，42.4，43.4，43.5，45.1，46.4，46.7，48.4，54.4，70.6，122.5，144.9，171.2，179.3，180.2；ESI-MS?m/z：583.4[M-H] -.
With 2-(β)-(4-benzyl ester-2,2-dimethyl succinic acid ester)-3-deoxidation oleanolic acid-28-benzyl ester is raw material, makes 2-(β)-O-(2 ', 2 '-dimethyl succinyl)-3-deoxidation oleanolic acid with reference to the method for embodiment 3. 1H?NMR(300MHz，C 5D 5N)?δppm：0.86(s，3H)，0.93(s，3H)，0.98(s，3H)，1.00(s，3H)，1.07(s，3H)，1.19(s，3H)，1.24(s，3H)，1.44(s，3H)，1.45(s，3H)，2.90(s，2H)，3.29(dd，J＝3.9Hz，13.7Hz，1H)，5.46(brs，2H)； 13C?NMR(300MHz，C 5D 5N)δ?ppm：17.2，17.5，18.9，23.8，24.0，25.7，25.8，26.3，28.3，31.0，32.5，33.1，33.3，33.7，34.4，37.4，40.1，40.7，42.1，42.5，43.5，43.9，45.0，46.5，46.8，48.5，55.0，70.7，122.6，124.2，144.9，173.8，176.4，180.1；ESI-MS?m/z：607.4[M+Na] +.
Embodiment 14
The preparation of 2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-methyl esters
With 2-(β)-hydroxyl-3-deoxidized Oleanolic Acid (0.05g), be dissolved among the DMF (1ml), add salt of wormwood (0.03g), drip methyl iodide (0.008ml), stirring at room adds entry (10ml) after 5 hours, with ethyl acetate extraction three times, organic layer with the saturated common salt water washing to neutral, anhydrous sodium sulfate drying, filter, concentrate, rapid column chromatography (petrol ether/ethyl acetate=7/1) gets 2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-methyl esters, white solid 49mg, yield 94.9%. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.73(s，3H)，0.89(s，3H)，0.92(s，6H)，1.00(s，3H)，1.12(s，3H)，1.18(s，3H)，2.85(dd，J＝3.4Hz，14Hz，1H)，4.08(d，J＝4.8Hz，1H)，5.30(brs，1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：16.8，18.5，19.0，23.1，23.4，23.6，24.6，25.9，27.6，30.0，30.7，32.4，32.5，32.7，33.0，33.1，33.9，37.8，39.6，41.4，41.9，45.8，46.6，46.8，47.2，48.0，51.5，53.5，67.7，122.6，143.7，178.3；ESI-MS?m/z：493.4[M+Na] +.
Embodiment 15
The preparation of 2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-ethyl ester
With 2-(β)-hydroxyl-3-deoxidized Oleanolic Acid and monobromethane is raw material, makes 2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-ethyl ester with reference to the method for embodiment 14. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.75(s，3H)，0.89(s，3H)，0.92(s，6H)，1.00(s，3H)，1.13(s，3H)，1.18(s，3H)，1.25(s，3H)，2.86(dd，J＝3.7Hz，13.8Hz，1H)，4.03-4.13(m，3H)，5.31(brs，1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：14.3，16.9，18.5，19.0，23.0，23.5，23.6，24.7，25.9，27.6，30.0，30.7，32.4，32.6，32.7，33.0，33.1，34.0，37.8，39.7，41.4，41.9，45.9，46.6，47.3，48.0，53.5，60.1，67.7，122.6，143.8，177.7；ESI-MS?m/z：507.5[M+Na] +.
Embodiment 16
The preparation of 2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-(2-bromine ethyl ester)
With 2-(β)-hydroxyl-3-deoxidized Oleanolic Acid and glycol dibromide is raw material, makes 2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-(2-bromine ethyl ester) with reference to the method for embodiment 14. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.75(s，3H)，090(s，3H)，0.93(s，3H)，1.00(s，3H)，1.14(s，3H)，1.18(s，3H)，1.25(s，3H)，2.88(dd，J＝3.5Hz，13.6Hz，1H)，3.50(t，J＝6.0Hz，2H)，4.06-4.10(m，1H)，4.29-4.37(m，2H)，5.33(t，J＝3.1Hz，1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：17.0，18.5，19.0，23.0，23.5，23.6，24.6，25.9，27.6，29.0，29.7，30.7，32.5，32.6，32.7，33.1，33.9，37.8，39.7，41.4，41.9，45.8，46.6，46.9，47.3，48.0，53.5，63.6，67.7，122.9，143.4，177.3；ESI-MS?m/z：601.3[M+K] +.
Embodiment 17
The preparation of 2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-ethyl acetate
With 2-(β)-hydroxyl-3-deoxidized Oleanolic Acid and ethyl bromoacetate is raw material, makes 2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-ethyl acetate with reference to the method for embodiment 14. 1H?NMR(300MHz，CDCl 3)δ?ppm0.74(s，3H)，090(s，3H)，0.93(s，6H)，1.00(s，3H)，1.13(s，3H)，1.18(s，3H)，1.27(t，J＝7.1Hz，3H)，2.88(dd，J＝4.0Hz，13.6Hz，1H)，4.08(brs，1H)，4.20(q，J＝7.1Hz，2H)，4.55(q，J＝15.7Hz，2H)，5.32(t，J＝3.4Hz，1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm14.1，16.8，18.5，19.0，23.2，23.5，23.6，24.6，25.8，27.6，29.7，30.7，32.2，32.5，32.7，33.0，33.1，33.9，37.8，39.7，41.4，41.9，45.9，46.6，46.8，47.3，48.1，53.5，60.5，61.2，67.7，122.8，143.5，168.1，177.0；ESI-MS?m/z：565.3[M+Na] +.
Embodiment 18
The preparation of 2-(β)-acetoxy-3-deoxidation-oleanolic acid-28-benzyl ester
With 2-(β)-hydroxyl-3-deoxidized-oleanolic acid benzyl ester (90mg), be dissolved in the pyridine (4ml), add acetic anhydride (1ml), stirring at room adds dilute hydrochloric acid and transfers pH=3 after 8 hours, use ethyl acetate extraction three times, organic layer washs with saturated sodium bicarbonate solution, the saturated common salt water washing is to neutral, and anhydrous sodium sulfate drying filters, concentrate, rapid column chromatography (petrol ether/ethyl acetate=30/1) gets white solid 76mg, yield 78.4%. 1H?NMR(300MHz，CDCl 3)δ?ppm0.65(s，3H)，092(s，3H)，0.94(s，6H)，1.01(s，3H)，1.13(s，3H)，1.15(s，3H)，2.04(s，3H)，2.93(dd，J＝4.1Hz，13.7Hz，1H)，5.04-5.15(m，3H)，5.31(t，J＝3.5Hz，1H)，7.28-7.38(m，5H)； 13C?NMR(300MHz，CDCl 3)δ?ppm17.0，17.1，18.7，21.5，23.2，23.5，23.7，23.8，26.0，27.7，30.8，32.5，32.7，33.1，33.4，34.1，37.4，39.7，41.6，42.0，43.5，46.0，46.9，48.2，54.6，66.0，70.7，122.7，127.9，128.1，128.4，136.6，143.8，170.4，177.4；ESI-MS?m/z：611.5[M+Na] +.
Embodiment 19
The preparation of 2-(β)-acetoxy-3-deoxidation-oleanolic acid
With 2-(β)-acetoxy-3-deoxidation-oleanolic acid-28-benzyl ester is raw material, makes 2-(β)-acetoxy-3-deoxidation-oleanolic acid with reference to the method for embodiment 3. 1H?NMR(300MHz，CDCl 3)δ?ppm0.77(s，3H)，091(s，3H)，0.92(s，3H)0.93(s，3H)，0.98(s，3H)，1.13(s，3H)，1.14(s，3H)，2.00(s，3H)，2.93(dd，J＝4.4Hz，13.6Hz，1H)，5.05-5.10(m，1H)，5.29(t，J＝3.4Hz，1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm17.1，18.7，21.5，23.1，23.5，23.6，23.7，26.0，27.7，30.7，32.5，32.6，33.1，33.4，33.9，37.4，39.7，41.3，41.9，43.5，45.9，46.6，48.2，54.6，70.7，122.9，143.6，170.4，182.2，208.8；ESI-MS?m/z：521.4[M+Na] +.
Embodiment 20
The preparation of 2-(β)-benzoyloxy-3-deoxidation-oleanolic acid-28-benzyl ester
With 2-(β)-hydroxyl-3-deoxidized-oleanolic acid benzyl ester and Benzoyl chloride is raw material, makes 2-(β)-benzoyloxy-3-deoxidation-oleanolic acid-28-benzyl ester with reference to the method for embodiment 18. 1H?NMR(300MHz，CDCl 3)δ?ppm0.64(s，3H)，090(s，3H)，0.92(s，3H)，0.96(s，3H)，1.08(s，3H)，1.15(s，3H)，1.26(s，3H)，2.93(m，1H)，5.01-5.13(m，2H)，5.29-5.39(m，2H)，7.25-7.34(m，5H)，7.41-7.47(m，2H)，7.52-7.55(m，1H)，8.00-8.03(m，2H)； 13C?NMR(300MHz，CDCl 3)δ?ppm17.0，17.1，18.7，23.2，23.5，23.7，23.8，26.0，27.6，30.7，32.5，32.7，33.1，33.6，34.0，37.2，39.7，41.5，42.0，43.5，43.8，46.0，46.9，48.2，54.9，66.0，71.5，122.7，127.9，128.0，128.4，129.5，131.1，132.7，136.6，143.8，160.7，166.2，177.4.
Embodiment 21
The preparation of 2-(β)-benzoyloxy-3-deoxidation-oleanolic acid
With 2-(β)-benzoyloxy-3-deoxidation-oleanolic acid-28-benzyl ester is raw material, makes 2-(β)-benzoyloxy-3-deoxidation-oleanolic acid with reference to the method for embodiment 3. 1H?NMR(300MHz，CDCl 3)δ?ppm0.78(s，3H)，091(s，3H)，0.93(s，3H)，0.97(s，3H)，1.08(s，3H)，1.15(s，3H)，1、24(s，3H)，2.84(m，1H)，5.29(brs，2H)，5.38(t，J＝3.87Hz，1H)，7.40-7.46(m，2H)，7.51-7.57(m，1H)，7.99-8.03(m，2H)； 13C?NMR(300MHz，CDCl 3)δ?ppm17.1，17.2，18.7，23.1，23.5，23.6，23.8，26.0，27.7，29.7，30.7，32.5，32.6，32.7，33.0，33.6，33.9，37.3，39.7，41.3，42.0，43.5，43.8，46.0，46.6，48.2，54.9，71.5，122.9，128.4，129.5，131.1，132.6，143.6，166.2，182.0.
Embodiment 22
The preparation of 1-alkene-2-hydroxyl-3-carbonyl-28-trityl ether trochol
3-carbonyl-28-trityl ether trochol (1.14g) is dissolved in the trimethyl carbinol (80ml), adds potassium tert.-butoxide (0.821g), 30 ℃ are stirred down, and the 10h afterreaction finishes.The evaporate to dryness trimethyl carbinol, under the ice bath, 1N HCl neutralization reaction liquid is to PH ≈ 5.Ethyl acetate extraction (20ml * 2,15ml * 2), saturated sodium bicarbonate solution and saturated common salt water washing organic layer are to neutrality, anhydrous Na SO 4Drying is filtered, and concentrates rapid column chromatography (petrol ether/ethyl acetate=80:1), get 1-alkene-2-hydroxyl-3-carbonyl-28-trityl ether trochol, white powder 960mg, yield 82.76%. 1H?NMR(300MHz，CDCl 3)δppm：0.56(s，3H)，0.88(s，3H)，1.05(s，3H)，1.08(s，3H)，1.12(s，3H)，1.63(s，3H)，2.17-2.26(m，3H)，2.93，3.11(d，J＝8.8Hz，each?1H)，4.54，4.59(d，J＝2.2Hz，each?1H)，5.85(s，1H，disappear?after?D20?exchange)，6.37(s，1H)，7.47-7.50(m，6H)，7.26-7.33(m，6H)，7.22-7.25(m，3H)； 13C?NMR(300MHz，CDCl 3)δppm：14.1，14.6，16.3，18.7，19.1，20.1，21.0，22.7，25.0，26.8，27.1，29.3，29.6，29.7，29.9，30.0，31.9，33.8，35.2，37.4，38.5，41.4，42.8，43.9，45.5，47.5，47.8，48.8，53.9，59.6，85.9，109.5，126.8，127.7，128.8，143.8，144.5，150.5，201.2；ESI-MSm/z：719.5[M+Na] +.
Embodiment 23
The preparation of 2-(β)-hydroxyl-28-trityl ether trochol
1-alkene-2-hydroxyl-3-carbonyl-28-trityl ether trochol (900mg) is dissolved among the THF (25ml), add ethanol (5ml), ice bath is cooled to 0 ℃, slowly add sodium borohydride (136mg), naturally be warming up to room temperature, the 1h afterreaction finishes, the most of organic solvent of evaporated under reduced pressure, and 1N HCl neutralization reaction liquid is to PH ≈ 5.Ethyl acetate extraction (20ml * 2,15ml * 2), saturated sodium bicarbonate solution and saturated common salt water washing organic layer are to neutrality, anhydrous Na SO 4Drying is filtered, and concentrates, and (petrol ether/ethyl acetate=8:1) get 2-(β)-hydroxyl-28-trityl ether trochol, white powder 650mg, productive rate are 65% to rapid column chromatography. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.53(s，3H)，0.88(s，3H)，0.96(s，6H)，1.07(s，3H)，1.63(s，3H)，2.04-2.23(m，6H)，2.90，3.13(d，J＝8.8Hz，each?1H)，3.15(d，J＝3.4Hz，1H)，4.02-4.03(m，1H)，4.51，4.58(d，J＝2.0Hz，each?1H)，7.46-7.50(m，6H)，7.26-7.32(m，6H)，7.21-7.24(m，3H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：14.7，15.9，17.0，17.1，18.1，19.1，20.9，25.2，26.8，29.4，29.6，29.7，29.9，30.2，34.1，35.2，36.8，37.2，38.1，40.7，42.6，44.4，47.6，47.7，48.9，50.8，55.2，59.6，71.2，85.9，109.3，126.8，127.7，128.8，144.5，150.8；ESI-MS?m/z：723.5[M+Na] +.
Embodiment 24
The preparation of 2-carbonyl-3-deoxidation-28-trityl ether trochol
2-(β)-hydroxyl-28-trityl ether trochol (500mg) is dissolved in the pyridine (3ml), adds Tosyl chloride (546.3mg), stirring reaction under 60 ℃ of temperature.The 12h afterreaction finishes, and is cooled to room temperature, and 1N HCl neutralization reaction liquid is to PH ≈ 5, and ethyl acetate extraction (20ml * 2,15ml * 2), saturated sodium bicarbonate solution and saturated common salt water washing organic layer are extremely neutral, anhydrous Na SO 4Drying is filtered, and concentrates, and (petrol ether/ethyl acetate=80:1) get 2-carbonyl-3-deoxidation-28-trityl ether trochol, white powder 321mg, productive rate are 72.9% to rapid column chromatography. 1H?NMR(300MHz，CDCl 3)δppm：0.50(s，3H)，0.76(s，3H)，0.85(s，3H)，0.93(s，3H)，1.03(s，3H)，1.63(s，3H)，1.82-1.87(m，1H)，2.09-2.32(m，6H)，2.90，3.11(d，J＝8.8Hz，each?1H)，4.52，4.58(d，J＝2.0Hz，each?1H)，7.46-7.49(m，6H)，7.25-7.32(m，6H)，7.19-7.24(m，3H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：14.7，15.517.1，19.0，19.1，20.9，23.1，25.0，26.9，29.6，29.7，29.9，30.1，33.3，33.7，35.2，37.2，39.0，40.0，42.6，42.9，47.6，47.7，48.8，50.0，55.6，56.0，56.5，59.6，85.9，109.5，126.8，127.7，128.8，144.5，150.6，212.2；ESI-MS?m/z：721.3[M+K] +.
Embodiment 25
2-is hydroxyl-3-deoxidized-preparation of 28-trityl ether trochol
2-carbonyl-3-deoxidation-28-trityl ether trochol (1g) is dissolved among the THF (15ml), adds 3ml ethanol, ice bath slowly adds sodium borohydride (0.15g) down, is warming up to room temperature naturally, and the 1h afterreaction finishes.The most of organic solvent of evaporated under reduced pressure, 1N HCl neutralization reaction liquid is to PH ≈ 5.Ethyl acetate extraction (50ml * 2,25ml * 1,15ml * 1), saturated sodium bicarbonate solution and saturated common salt water washing organic layer are to neutrality, anhydrous Na SO 4Drying is filtered, and concentrates, and (petrol ether/ethyl acetate=25:1) get 2-(β)-hydroxyl-3-deoxidized-28-trityl ether trochol, white powder 750mg, productive rate are 75% to rapid column chromatography. 1H NMR (300MHz, CDCl 3) δ ppm:0.52 (s, 3H), 0.89 (s, 3H), 0.90 (s, 3H), 0.98 (s, 3H), 1.01 (s, 3H), 1.64 (s, 3H), 1.82-1.87 (m, 1H), 2.17-2.20 (m, 3H), 2.90, (3.14 d, J=8.8Hz, each 1H), and 3.99-4.02 (m, 1H), 4.52,4.58 (d, J=2.1Hz, each1H), 7.47-7.49 (m, 6H), and 7.25-7.32 (m, 6H), 7.22-7.24 (m, 3H); 13C NMR (300MHz, CDCl 3) δ ppm:14.7,15.7,19.1,19.7,21.2,24.8,25.3,26.8,29.9,30.1,32.5,32.8,33.6,35.2,37.4,38.2,40.8,42.5,46.3,47.6,47.7,48.2,48.9,50.8,52.7,59.6,67.5,85.8,109.3,126.8,127.7,128.8,144.5,150.8; ESI-MS m/z:723.4[M+K] +. obtain 2-(α)-hydroxyl-3-deoxidized-28-trityl ether trochol simultaneously, white powder 100mg, isolated yield is 10%. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.50(s，3H)，0.79(s，3H)，0.82(s，3H)，0.89(s，3H)，0.90(s，3H)，1.63(s，3H)，1.95-1.98(m，1H)，2.12-2.23(m，3H)，2.90，3.12(d，J＝8.8Hz，each?1H)，3.79-3.87(m，1H)，4.52，4.57(d，J＝2.1Hz，each?1H)，7.46-7.49(m，6H)，7.25-7.32(m，6H)，7.19-7.24(m，3H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：14.7，15.7，17.1，18.4，19.1，20.7，22.4，25.1，26.9，29.9，30.1，33.4，34.0，34.9，35.2，37.2，39.2，40.8，42.5，47.6，47.8，48.9，49.7，50.3，51.2，55.8，59.6，65.3，85.8，109.4，126.8，127.7，128.8，144.5，150.7；ESI-MS?m/z：723.4[M+K] +.
Embodiment 26
The preparation of 2-(β)-hydroxyl-3-deoxidized trochol
2-(β)-hydroxyl-3-deoxidized-28-trityl ether trochol (50mg) is dissolved in the dehydrated alcohol (5ml), adds PPTS (91.25mg), 70 ℃ are stirred down, and raw material disappears behind the 20h.Remove ethanol under reduced pressure, with frozen water 20ml, ethyl acetate extraction (25ml * 2,15ml * 2), saturated common salt water washing organic layer, anhydrous Na SO 4Dry filter concentrates, and (petrol ether/ethyl acetate=10:1), get the hydroxyl-3-deoxidized trochol of 2-, white powder 32mg, productive rate are 99% to rapid column chromatography. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.93(s，3H)，0.98(s，6H)，1.03(s，3H)，1.06(s，3H)，1.71(s，3H)，1.92-1.98(m，3H)，2.35-2.44(m，1H)，3.34，3.80(d，J＝10.8Hz，each?1H)，4.00-4.11(m，1H)，4.60，4.70(d，J＝1.8Hz，each?1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：14.1，14.8，15.9，19.2，19.8，21.4，22.7，24.8，25.5，27.1，29.3，29.4，29.7，29.7，29.9，31.9，32.6，32.9，33.8，34.0，37.6，38.3，41.2，42.9，46.5，47.8，47.9，48.4，48.9，51.0，52.9，60.6，67.5，109.3，150.5；ESI-MS?m/z：465.4[M+Na] +.
Embodiment 27
The preparation of 2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation-28-trityl ether trochol
2-(β)-hydroxyl-3-deoxidized-28-trityl ether trochol (150mg) is dissolved in the pyridine (2ml), adds DMAP (53.44mg), 2,2 one dimethyl succinic anhydrides (112.3mg), raw material disappears behind 95 ℃ of following 20h of stirring.1N HCl neutralization reaction liquid is to PH ≈ 5.Ethyl acetate extraction (50ml * 2,25ml * 1,15ml * 1), saturated sodium bicarbonate solution and saturated common salt water washing organic layer are to neutrality, anhydrous Na SO 4Drying concentrates, and (petrol ether/ethyl acetate=50:1), get 2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation-28-trityl ether trochol, white powder 100mg, productive rate are 56.2% to rapid column chromatography. 1H?NMR(300MHz，C 5D 5N)δ?ppm：0.70(s，3H)，0.87(s，3H)，0.91(s，3H)，1.02(s，3H)，1.09(s，3H)，1.52(s，3H)，1.53(s，3H)，1.71(s，3H)，2.34-2.39(m，3H)，2.87(s，2H)，3.15，3.49(d，J＝8.8Hz，each?1H)，4.71，4.75(d，J＝2.0Hz，each?1H)，5.29(m，1H)，7.69-7.72(m，6H)，7.38-7.46(m，6H)，7.28-7.33(m，3H)； 13C?NMR(300MHz，C 5D 5N)δ?ppm：14.0，14.6，15.9，18.7，18.9，19.0，21.0，22.7，24.1，25.4，25.8，27.1，29.3，29.3，29.7，30.0，31.9，32.5，32.6，33.8，35.3，37.3，37.6，40.6，40.9，42.7，42.9，44.1，44.9，47.8，49.0，50.7，53.4，59.7，70.4，86.2，109.7，127.1，128.0，129.0，134.4，134.6，144.9，150.7，171.0，179.0；ESI-MS?m/z：835.5[M+Na] +.
Embodiment 28
The preparation of 2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation trochol
2-(β)-(3-carboxyl-3-methyl isophthalic acid-butyryl acyloxy)-3-deoxidation-28-trityl ether trochol (80mg) is dissolved in the dehydrated alcohol (5ml), adds PPTS (84.3mg), raw material disappears behind 70 ℃ of following 20h of stirring.Remove ethanol under reduced pressure, with frozen water 20ml, ethyl acetate extraction (25ml * 2,15ml * 2), saturated common salt water washing organic layer, anhydrous Na SO 4Drying concentrates, and (petrol ether/ethyl acetate=4:1), get 2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation trochol, white powder 42mg, productive rate are 75% to rapid column chromatography. 1H?NMR(300MHz，C 5D 5N)δ?ppm：0.88(s，3H)，0.97(s，3H)，0.991(s，3H)，1.00(s，3H)，1.09(s，3H)，1.54(s，3H)，1.55(s，3H)，1.78(s，3H)，2.1-2.18(m，1H)，2.37-2.45(m，2H)，2.57-2.65(m，1H)，2.88(s，2H)，3.64，4.07(d，J＝8.8Hz，each?1H)，4.77，4.90(d，J＝2.0Hz，each?1H)，5.30(m，1H)； 13C?NMR(300MHz，C 5D 5N)δ?ppm：14.9，16.1，18.9，19.1，19.3，21.5，24.4，25.8，26.0，26.1，27.6，30.0，30.1，30.5，32.8，32.9，34.1，34.9，37.8，38.0，40.9，41.4，43.2，43.2，44.5，45.2，48.4，48.6，49.2，51.2，53.8，59.6，70.1，109.9，151.4，171.3，179.3；ESI-MS?m/z：593.5[M+Na] +.
Embodiment 29
The preparation of 2-(β)-acetoxy-3-deoxidation-28-trityl ether trochol
With 2-(β)-hydroxyl-3-deoxidized-28-trityl ether trochol and diacetyl oxide is raw material, makes 2-(β)-acetoxy-3-deoxidation-28-trityl ether trochol with reference to the method for embodiment 27. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.54(s，3H)，0.89(s，3H)，0.91(s，3H)，0.95(s，3H)，0.98(s，3H)，1.66(s，3H)，1.98(s，3H)，2.90，3.14(d，J＝8.7Hz，each?1H)，4.51，4.57(brs，each?1H)，5.05(m，1H)，7.19-7.33(m，9H)，7.47-7.50(m，6H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：14.8，15.9，18.5，18.9，19.1，21.2，21.5，24.0，25.4，27.0，30.0，30.3，32.7，32.8，33.8，35.3，37.5，37.8，41.0，42.8，43.1，44.3，47.7，47.8，49.0，50.9，53.7，59.8，70.7，86.0，109.4，126.8，127.7，128.9，144.6，150.8，170.4.
Embodiment 30
The preparation of 2-(β)-acetoxy-3-deoxidation trochol
With 2-(β)-acetoxy-3-deoxidation-28-trityl ether trochol is raw material, makes 2-(β)-acetoxy-3-deoxidation trochol with reference to the method for embodiment 28. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.92(s，3H)，0.95(s，3H)，0.97(s，3H)，1.03(s，3H)，1.04(s，3H)，1.67(s，3H)，2.00(s，3H)，2.33-2.43(m，1H)，3.33，3.79(d，J＝10.8Hz，each?1H)，4.58，4.67(brs，each?1H)，5.05(m，1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：14.8，16.0，18.4，18.6，18.9，19.1，21.3，21.5，24.0，25.5，27.1，29.3，29.9，32.7，32.9，33.9，34.1，37.5，37.8，41.2，43.0，43.1，44.3，47.9，48.9，51.0，53.8，58.5，60.7，70.7，109.7，150.4，170.4.
Embodiment 31
The preparation of 2-carbonyl-3-deoxidation-28-acetic ester trochol
2-carbonyl-3-deoxidation-28-trityl ether trochol (600mg) is dissolved in the Glacial acetic acid (4ml), is heated to 60 ℃, the 12h afterreaction finishes.Remove solvent under reduced pressure, (petrol ether/ethyl acetate=15:1), get 2-carbonyl-3-deoxidation-28-acetic ester trochol, white powder 300mg, productive rate are 70.8% to rapid column chromatography. 1H?NMR(500MHz，CDCl 3)δ?ppm：0.84(s，3H)，0.87(s，3H)，1.01(s，3H)，1.04(s，3H)，1.05(s，3H)，1.68(s，3H)，2.06(s，3H)，2.13-2.16(m，1H)，2.24-2.27(m，1H)，2.42-2.45(m，1H)，3.85，4.26(d，J＝8.8Hz，each?1H)，4.60，4.69(d，J＝2.0Hz，each1H)； 13C?NMR(500MHz，CDCl 3)δ?ppm：14.8，15.7，17.2，19.0，19.2，20.9，21.0，23.1，25.1，27.1，29.6，29.8，37.5，39.0，41.3，42.8，42.9，46.3，47.7，48.8，50.1，55.7，56.1，56.5，62.7，109.9，149.9，171.5，212.2；ESI-MS?m/z：483.5[M+H] +.
Embodiment 32
The preparation of 2-carbonyl-3-deoxidation trochol
2-carbonyl-3-deoxidation-28-acetic ester trochol (300mg) is dissolved among the THF (6ml), adds methyl alcohol 4ml, drip 4N NaOH solution, room temperature reaction 2h.The evaporate to dryness organic solvent, under the ice bath, 1N HCl neutralization reaction liquid is to PH ≈ 5.Ethyl acetate extraction (50ml * 2,25ml * 1,15ml * 1), saturated sodium bicarbonate solution and saturated common salt water washing organic layer are to neutrality, anhydrous Na SO 4Drying concentrates, and (petrol ether/ethyl acetate=8:1), get 2-carbonyl-3-deoxidation trochol, white powder 260mg, productive rate are 96.7% to rapid column chromatography. 1H?NMR(300MHz，CDCl 3)δ?ppm：0.80(s，3H)，0.83(s，3H)，1.02(s，3H)，1.03(s，3H)，1.05(s，3H)，1.68(s，3H)，2.06(s，3H)，1.88-1.93(m，4H)，2.16-2.17(m，1H)，2.24-2.34(m，1H)，2.34-2.39(m，2H)，3.34，3.79(d，J＝8.8Hz，each?1H)，4.59，4.68(d，J＝2.0Hz，each?1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：14.8，15.7，17.2，19.1，19.2，21.1，23.1，25.2，27.2，29.2，29.8，33.4，33.8，34.0，37.3，39.0，41.4，42.9，43.0，47.8，47.9，48.8，50.2，55.8，56.2，56.5，60.6，109，8，150.3，212.0；ESI-MS?m/z：441.3[M+H] +.
Embodiment 33
The preparation of 2-(β)-hydroxyl-3-deoxidized white birch acid
The hydroxyl-3-deoxidized trochol of 2-(β) (100mg) is dissolved in the methylene dichloride (5ml), with the KBr of catalytic amount, Bu 4N +Br -, adding dichloromethane solution among the TEMPO (10.6mg) water-soluble (0.8ml), 5% sodium hydrogen carbonate solution (0.7ml) adds in the reaction solution again.Ice bath slowly drips chlorine bleach liquor 1ml down.Naturally be warming up to room temperature, the 20h afterreaction is complete.Tell organic layer, after the saturated common salt water washing 2 times, directly drip sodium chlorite solution's (25%) 1.5ml.Half an hour, afterreaction was complete, added saturated sodium sulfite solution 5ml quencher reaction.Remove ethyl acetate extraction behind most of organic solvent under reduced pressure, saturated common salt water washing organic layer 2 times.Anhydrous sodium sulfate drying filters, and concentrates rapid column chromatography (petrol ether/ethyl acetate=4:1), get the hydroxyl-3-deoxidized white birch acid of 2-(β), white solid 50mg, productive rate 48.5%. 1HNMR(300MHz，C 5D 5N)δ?ppm：0.89(s，3H)，0.99(s，3H)，1.01(s，3H)，1.06(s，3H)，1.19(s，3H)，1.75(s，3H)，2.15-2.21(m，2H)，2.44-2.71(m，2H)，3.41-3.49(m，1H)，4.28(m，1H)，4.86，4.69(d，J＝2.0Hz，each?1H)； 13C?NMR(300MHz，CDCl 3)δ?ppm：15.00，16.4，19.5，19.6，21.8，24.9，26.4，30.3，31.4，33.0，33.1，33.2，34.6，37.6，38.5，38.9，41.4，42.6，43.1，47.5，47.8，48.7，50.0，51.6，54.1，56.8，66.7，109.8，151.4；ESI-MS?m/z：455.4[M-H] -.

Claims (10)

1. the pentacyclic triterpenoid shown in general formula I or the II or its pharmacy acceptable salt or ester:
Figure A200710026109C00021
R wherein 1Independent hydrogen, the OR of representing 9, NHR 9, N (R 10) 2, SO 2NH 2, NHOR 9, NH 2NHR 9R 2Independent hydrogen, the OR of representing 9, NHR 9, N (R 10) 2, SO 2NH 2, NHOR 9, NH 2NHR 9Perhaps R 1With R 2Represent O or NOR together 9
R 3Represent hydrogen or methyl, R 4Represent hydrogen or methyl, and, R worked as 3When representing hydrogen, R 4Represent methylidene only; Work as R 3During represent methylidene, R 4Only represent hydrogen;
R 5Represent CH 3, CH 2OR 9, COOR 10, CONHR 9, CON (R 10) 2, NHR 9
R 6Independent hydrogen, the OR of representing 9, NHR 9, N (R 10) 2, SO 2NH 2, NHOR 9, NH 2NHR 9R 7Independent hydrogen, the OR of representing 9, NHR 9, N (R 10) 2, SO 2NH 2, NHOR 9, NH 2NHR 9Perhaps R 6With R 7Represent O or NOR together 9
R 8Represent CH 3, CH 2OR 9, COOR 10, CONHR 9, CON (R 10) 2, NHR 9
R 9Represent hydrogen or R 10, R 10CO, R 10SO 2
R 10Represent straight or branched alkane, alkene, alkynes, phenyl, benzyl, the naphthyl non-replacement or that X replaces of 1～10 carbon;
X represents H, F, Cl, Br, I, CN, NO 2, NH 2, CF 3, SH, OH, OCH 3, OC 2H 5, COOH, COOCH 3, COOC 2H 5, 1～10 carbon straight or branched alkane, alkene, alkynes, phenyl, benzyl, naphthyl.
2. the compound of claim 1 is characterized in that:
R 1Independent hydrogen, the OR of representing 9R 2Independent hydrogen, the OR of representing 9Perhaps R 1With R 2Represent O or NOR together 9
R 3Represent hydrogen or methyl, R 4Represent hydrogen or methyl, and, R worked as 3When representing hydrogen, R 4Represent methylidene only; Work as R 3During represent methylidene, R 4Only represent hydrogen;
R 5Represent CH 3, CH 2OR 9, COOR 10
R 6Independent hydrogen, the OR of representing 9R 7Independent hydrogen, the OR of representing 9Perhaps R 6With R 7Represent O or NOR together 9
R 8Represent CH 3, CH 2OR 9, COOR 10
R 9Represent hydrogen or R 10, R 10CO;
R 10Represent straight or branched alkane, alkene, alkynes, phenyl, benzyl, the naphthyl non-replacement or that X replaces of 1～10 carbon;
X represents H, F, Cl, Br, I, CN, NO 2, NH 2, CF3, SH, OH, OCH 3, OC 2H 5, COOH, COOCH 3, COOC 2H 5, 1～10 carbon straight or branched alkane, alkene, alkynes, phenyl, benzyl, naphthyl.
3. the compound of claim 2 is the compound of following arbitrary structure:
2-carbonyl-3-deoxidation Oleanolic Acid-28-benzyl ester
2-carbonyl-3-deoxidation ursolic acid-28-benzyl ester
2-carbonyl-3-deoxidation Oleanolic Acid
2-carbonyl-3-deoxidation ursolic acid
2-oximido-3-deoxidation Oleanolic Acid-28-benzyl ester
2-oximido-3-deoxidation ursolic acid-28-benzyl ester
2-oximido-3-deoxidation Oleanolic Acid
2-oximido-3-deoxidation ursolic acid
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-benzyl ester
2-(β)-hydroxyl-3-deoxidized ursolic acid-28-benzyl ester
2-(α)-hydroxyl-3-deoxidized oleanolic acid-28-benzyl ester
2-(α)-hydroxyl-3-deoxidized ursolic acid-28-benzyl ester
2-(β)-hydroxyl-3-deoxidized Oleanolic Acid
2-(β)-hydroxyl-3-deoxidized ursolic acid
2-(α)-hydroxyl-3-deoxidized oleanolic acid
2-(α)-hydroxyl 3-deoxidation ursolic acid
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-methyl esters
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-ethyl ester
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-propyl ester
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-butyl ester
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-allyl ester
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-(2-bromine ethyl ester)
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-(3-bromine propyl ester)
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-(4-bromine butyl ester)
2-(β)-hydroxyl-3-deoxidized oleanolic acid-28-ethyl acetate
2-(β)-acetoxy-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-propionyloxy-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-butyryl acyloxy-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-benzoyloxy-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-to tert.-butylbenzene methanoyl-3-deoxidation-oleanolic acid-28-benzyl ester
2-(β)-O-succinyl-3-deoxidation oleanolic acid-28-benzyl ester
2-(β)-acetoxy-3-deoxidation-oleanolic acid
2-(β)-propionyloxy-3-deoxidation-oleanolic acid
2-(β)-butyryl acyloxy-3-deoxidation-oleanolic acid
2-(β)-benzoyloxy-3-deoxidation-oleanolic acid
2-(β)-to tert.-butylbenzene methanoyl-3-deoxidation-oleanolic acid
2-(β)-O-succinyl-3-deoxidation oleanolic acid
2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation oleanolic acid
2-(β)-O-(2 ', 2 '-dimethyl succinyl)-3-deoxidation oleanolic acid
1-alkene-2-hydroxyl-3-carbonyl-28-trityl ether trochol
2-(β)-hydroxyl-28-trityl ether trochol
2-carbonyl-3 deoxidations-28-trityl ether trochol
2-carbonyl-3-deoxidation-28-acetic ester trochol
2-carbonyl-3-deoxidation trochol
2-(β)-hydroxyl-3-deoxidized-28-trityl ether trochol
2-(α)-hydroxyl-3-deoxidized-28-trityl ether trochol
2-(β)-hydroxyl-3-deoxidized trochol
2-(α)-hydroxyl-3-deoxidized trochol
2-(β)-acetoxy-3-deoxidation-28-trityl ether trochol
2-(β)-butyryl acyloxy-3-deoxidation-28-trityl ether trochol
2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation-28-trityl ether trochol
2-(β)-O-(2 ', 2 '-dimethyl succinyl)-3-deoxidation-28-trityl ether trochol
2-(β)-acetoxy-3-deoxidation trochol
2-(β)-propionyloxy-3-deoxidation trochol
2-(β)-butyryl acyloxy-3-deoxidation trochol
2-(β)-benzoyloxy-3-deoxidation trochol
2-(β)-O-(3 ', 3 '-dimethyl succinyl)-3-deoxidation trochol
2-(β)-O-(2 ', 2 '-dimethyl succinyl)-3-deoxidation trochol
2-carbonyl-3-deoxidation white birch acid
2-(β)-hydroxyl-3-deoxidized white birch acid
4. the compound of claim 1, wherein pharmacy acceptable salt is sodium salt, sylvite, ammonium salt, organic amine salt or basic aminoacids (as: Methionin and the arginine) salt of compound shown in general formula I or the II.Its pharmacy acceptable salt also comprises the acid salt that compound shown in general formula I or the II and following acid form: hydrochloric acid, Hydrogen bromide, sulfuric acid, carbonic acid, citric acid, tartrate, phosphoric acid, lactic acid, pyruvic acid, acetate, toxilic acid, methylsulfonic acid, Phenylsulfonic acid or tosic acid.
5. the preparation method of the compound of claim 1 may further comprise the steps:
(1) preparation of 2-carbonyl-3-deoxidation pentacyclic triterpene compound:
Figure A200710026109C00041
In the following formula, R 3, R 4, R 5And R 8Described as defined above.Under base catalysis, (2 β, 3 β)-2,3-dihydroxyl pentacyclic triterpene compound and Tosyl chloride or benzene sulfonyl chloride reaction obtain 2-carbonyl-3-deoxidation pentacyclic triterpene compound.The alkali that is adopted comprises pyridine, triethylamine, salt of wormwood, yellow soda ash, sodium bicarbonate, saleratus, sodium hydroxide or potassium hydroxide, preferentially adopts pyridine.The solvent that is adopted comprises pyridine, methylene dichloride, 1,2-ethylene dichloride, chloroform, toluene, N, dinethylformamide (DMF), N, N-N,N-DIMETHYLACETAMIDE (DMA), acetonitrile, tetrahydrofuran (THF) or dioxane, perhaps with the optional mixed solvent of forming of these solvents, preferential pyridine, 1,2-ethylene dichloride, toluene, N, dinethylformamide or the tetrahydrofuran (THF) of adopting.Temperature of reaction can be controlled in 0 degree to 150 degree, preferentially adopts room temperature to 80 degree as temperature of reaction.
(2) preparation of 2-oximido-3-deoxidation pentacyclic triterpene compound:
In the following formula, R 3, R 4, R 5And R 8Described as defined above.2-carbonyl in the following formula-3-deoxidation pentacyclic triterpene compound and oxammonium hydrochloride react under base catalysis, generate 2-oximido-3-deoxidation pentacyclic triterpene compound.The alkali that is adopted comprises pyridine, triethylamine, salt of wormwood, yellow soda ash, sodium bicarbonate, saleratus, sodium hydroxide or potassium hydroxide, preferentially adopts pyridine.The solvent that is adopted comprises pyridine, methylene dichloride, 1,2-ethylene dichloride, chloroform, toluene, N, dinethylformamide (DMF), N, N-N,N-DIMETHYLACETAMIDE (DMA), acetonitrile, tetrahydrofuran (THF) or dioxane, perhaps with the optional mixed solvent of forming of these solvents, preferential pyridine, 1,2-ethylene dichloride, toluene, N, N-methylformamide or the tetrahydrofuran (THF) of adopting.Temperature of reaction can be controlled in 0 degree to 150 degree, preferentially adopts room temperature to 80 degree as temperature of reaction.
(3) preparation of the hydroxyl-3-deoxidized pentacyclic triterpene compound of 2-:
Figure A200710026109C00052
In the following formula, R 3, R 4, R 5And R 8Described as defined above.2-carbonyl in the following formula-3-deoxidation pentacyclic triterpene compound generates the hydroxyl-3-deoxidized pentacyclic triterpene compound of 2-under the effect of reductive agent.The reductive agent that is adopted is selected from sodium borohydride, POTASSIUM BOROHYDRIDE, Virahol/aluminum isopropylate, borine/tetrahydrofuran (THF) or borine/dimethyl sulphide, preferentially adopts sodium borohydride (potassium).The solvent that is adopted is selected from the mixture of tetrahydrofuran (THF), ethanol, methyl alcohol, ether, t-butyl methyl ether, ethyl acetate, ethyl formate, methyl acetate, dioxane or above-mentioned solvent, preferentially adopts tetrahydrofuran (THF)/ethanol as reaction solvent.Temperature of reaction can be controlled in zero degree to 60 degree, preferentially adopt zero degree to room temperature as temperature of reaction.
(4) preparation of 2-O-acyl group-3-deoxidation pentacyclic triterpene compound:
Figure A200710026109C00061
In the following formula, R 3, R 4, R 5, R 8And R 10Described as defined above.According to the hydroxy esterification method of routine, the hydroxyl-3-deoxidized pentacyclic triterpene compound of the 2-in the following formula and various acyl chlorides, acid anhydrides or carboxylic acid reaction obtain 2-O-acyl group-3-deoxidation pentacyclic triterpene compound.
(5) preparation of 3-deoxidation pentacyclic triterpene-28-ester cpds:
Figure A200710026109C00062
In the following formula, R 1, R 2, R 3, R 4, R 6, R 7And R 10Described as defined above.According to the carboxyalkyl esterification process of routine, the 3-deoxidation pentacyclic triterpene in the following formula-28-acid and various halogenated alkane reactions obtain 3-deoxidation pentacyclic triterpene-28-ester cpds.
6. pharmaceutical composition wherein contains compound and pharmaceutically acceptable carrier shown in the general formula I for the treatment of significant quantity or the II.
7. each compound is used for preventing and treat the purposes of the medicine of diabetes, cardiovascular disorder, cerebrovascular disease and tumour in the claim 1 to 4 in preparation.
8. the purposes of claim 7, wherein diabetes are diabetes Bs.
9. the purposes of claim 7, wherein cardiovascular disorder is myocardial infarction, stenocardia, irregular pulse, coronary heart disease, atherosclerosis, heart failure, hypertension or pulmonary hypertension.
10. the purposes of claim 7, wherein cerebrovascular disease is apoplexy, cerebral infarction, cerebral infarction, cerebral ischemia or ischemia nerve degenerative diseases.
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