CN102924556A - (20S, 24R)-ocotillol type ginsenoside derivative having antibacterial activity and preparation method and application thereof - Google Patents
(20S, 24R)-ocotillol type ginsenoside derivative having antibacterial activity and preparation method and application thereof Download PDFInfo
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Abstract
本发明涉及有机合成和药物化学领域，具体涉及一类(20S，24R)-ocotillol型人参皂苷类衍生物，结构如通式(I)。本发明还公开了这些(20S，24R)-ocotillol型人参皂苷类衍生物的制备方法，含有它们的药物组合物及其抗细菌感染疾病用途。 The invention relates to the fields of organic synthesis and medicinal chemistry, in particular to a class of (20S, 24R)-ocotillol type ginsenoside derivatives, the structure of which is shown in general formula (I). The invention also discloses the preparation method of these (20S, 24R)-ocotillol type ginsenoside derivatives, the pharmaceutical composition containing them and the antibacterial infection disease application. 
Description
Technical field
The present invention relates to organic synthesis and pharmaceutical chemistry field, be specifically related to grand (ocotillol) type Hydrolizates of class Losec ladder, their preparation method contains their pharmaceutical composition and bacterial-infection resisting disease purposes thereof.
Background technology
Ginsenoside is distributed widely in the plant, and multiple physiologically active is arranged, as anticancer, and control cardiovascular and cerebrovascular diseases, step-down etc.Ginsenoside mainly is divided into four classes: 20 (S) protopanoxadiol type, 20 (S) Protopanaxatriol type, oleanane type and ocotillol type.At present, the content of ocotillol type ginsenoside in plant is few, and isolated yield is low, and its bibliographical information is less.We find early-stage Study, ocotillol type ginsenoside has preferably function of resisting myocardial ischemia (referring to Bi Y, Tian W J, Wang L, et al.Synthesis, structural determination and protective effects on cultured anoxia/reoxygeninjurymyocardiocytes of ocotillol-type derivatives[J] .Medicinal Plants Research, 2011,5:2424-2429).In order to explore widely pharmacologically active of ocotillol type ginsenoside, to enrich its clinical application, we are take 20 (S) protopanoxadiol as raw material, obtained with (20S, 24R)-epoxydammarane-3,12 by semi-synthetic, 25-triol is the ocotillol type ginsenoside of parent nucleus, and on this basis, its different loci is carried out structural modification, to obtaining to have multiple bioactive new drug candidate compound.
Summary of the invention
Easy to prepare for seeking, have multiple bioactive candidate compound, the present invention has found the ocotillol type Hydrolizates with anti-microbial activity of series of new, thereby a series of derivatives with general formula (I) structural performance are provided.These compounds all belong to new compound, and for synthetic first, its anti-microbial activity also belongs to first to be found.
The technical problem to be solved in the present invention is to seek the bioactive ocotillol type compound that has of new texture type.
For solving the problems of the technologies described above, the invention provides following technical scheme:
The compound or pharmaceutically acceptable salt thereof of general formula (I):
Wherein:
R
1Be selected from hydroxyl, oxo, hydroxyl oxime generation, acetoxyl group, acryloxy, 2,4-hexadiene acyloxy, hot acyloxy, mesyloxy, tolysulfonyl oxygen base, benzoyloxy, the o-methyl-benzene methanoyl, between toluyl oxygen base, to toluyl oxygen base, the O-methoxy benzoyloxy, the meta-methoxy benzoyloxy, to methoxybenzoyl oxygen base, adjacent chlorobenzoyl oxygen base, the m-chloro benzoyloxy, to chlorobenzoyl oxygen base, adjacent bromobenzene methanoyl, between the bromobenzene methanoyl, to the bromobenzene methanoyl, the o-trifluoromethyl benzoyloxy, the m-trifluoromethyl benzoyloxy, to the trifluoromethyl benzoyloxy, the ortho-nitrophenyl methanoyl, the m-nitro methanoyl, the p-nitrophenyl methanoyl, adjacent cyano group benzoyloxy, between the cyano group benzoyloxy, to the cyano group benzoyloxy, 3-pyridine methanoyl, phenylallene acyl-oxygen base, adjacent chlorobenzene acryloxy, O-methoxy phenylallene acyl-oxygen base, to the bromobenzene acryloxy, the estragole acyloxy, the p-nitrophenyl acryloxy, 2-furoyl oxygen base, 3-carboxyl propionyloxy, 3-carboxyl acryloxy, 4-carboxyl butyryl acyloxy, glycyl oxygen base, 4-piperidine formyl oxygen base, 2-carboxyl benzoyloxy, 2-(2-hydroxybenzoyl) oxygen base, β-D-glucopyanosyl base, β-D-glucopyanosyl base (1-2)-β-D-glucopyanosyl base.
R
2Be selected from hydrogen, hydroxyl, β-D-glucopyanosyl base, α-L-rhamnopyranosyl (1-2)-β-D-glucopyranosyl.
R
3Be selected from hydroxyl, oxo, acetoxyl group, 2-carboxyl benzoyloxy.
The compound or pharmaceutically acceptable salt thereof of aforementioned formula (I): R wherein
1Preferred representation hydroxy, 3-carboxyl propionyloxy, 3-carboxyl acryloxy, 4-carboxyl butyryl acyloxy, glycyl oxygen base, 4-piperidine formyl oxygen base, 2-carboxyl benzoyloxy, adjacent cyano group benzoyloxy, p-nitrophenyl acryloxy.
R
2The preferred hydrogen that represents.
R
3Preferred representation hydroxy, 2-carboxyl benzoyloxy.
Part of compounds of the present invention is:
(20S, 24R)-epoxy dammarane-3 beta, 12 β, 25-triol;
(20S, 24R)-epoxy dammarane-3 beta, 6 α, 12 β, 25-tetrol;
(20S, 24R)-epoxy dammarane-12 β, 25-glycol-3-ketone;
(20S, 24R)-epoxy dammarane-12 β, 25-glycol-3-ketoxime;
(20S, 24R)-epoxy dammarane-3 beta, 25-glycol-12-ketone;
(20S, 24R)-epoxy dammarane-25-alcohol-3, the 12-diketone;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-ethanoyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-acryl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-[3 β-O-(2E, 4E)-hexadiene acyl group]-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-capryloyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-benzoyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-O-methoxy benzoyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-is to anisoyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(the adjacent chlorobenzene formacyl of 3 β-O-)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-is to chlorobenzene formacyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(benzoyl bromide between 3 β-O-)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-p-nitrophenyl formyl radical)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-o-trifluoromethyl benzoyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-is to the trifluoromethyl benzoyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-o-hydroxy formyl radical)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-3-pyridine formyl radical)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-2-furancarbonyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-[3 β-O-(E)-phenylpropenoyl]-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-[3 β-O-(E)-adjacent chlorobenzene acryl]-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-[3 β-O-(E)-O-methoxy phenylpropenoyl]-dammarane;
(20S, 24R)-epoxy-12 β, the 25-dihydroxyl-[3 β-O-(E)-to the bromobenzene acryl]-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-[3 β-O-(E)-p-nitrophenyl acryl]-dammarane;
4-[(20S, 24R)-epoxy-12 β, 25-dihydroxyl-dammarane-3 beta-oxygen base]-the 4-oxo-butynic acid;
4-[(20S, 24R)-epoxy-12 β, 25-dihydroxyl-dammarane-3 beta-oxygen base]-4-oxo-2 (E)-alkene-butyric acid;
5-[(20S, 24R)-epoxy-12 β, 25-dihydroxyl-dammarane-3 beta-oxygen base]-4-oxo-valeric acid;
2-[(20S, 24R)-epoxy-12 β, 25-dihydroxyl-dammarane-3 beta-oxygen base]-carbonyl-phenylformic acid;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-glycyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-4-piperidine formyl base)-dammarane;
(20S, 24R)-epoxy-3 β, 25-dihydroxyl-(12 β-O-ethanoyl)-dammarane;
(20S, 24SR)-epoxy-3 β, 25-dihydroxyl-[12 β-O-(E)-phenylpropenoyl]-dammarane;
2-[(20S, 24R)-epoxy-3 β, 25-dihydroxyl-dammarane-12 β-oxygen base]-carbonyl-phenylformic acid;
(20S, 24R)-epoxy-25-hydroxyl-(3 β, 12 β-O-two adjacent carboxylbenzoyls)-dammarane.
The present invention includes the compound or its salt of general formula (I), upper respiratory tract infection, urinary tract infection enteritis, diarrhoea and septicemia etc. that its preparation method and treatment gram-positive microorganism and gram positive bacterial infection cause.
The compound of general formula (I) is synthetic preparation as follows:
A. take 20 (S)-protopanoxadiols or 20 (S)-Protopanaxatriols as raw material, acetylize protection hydroxyl.
B. metachloroperbenzoic acid carries out 20,24-epoxidation under cryosel is bathed.
C. the hydrolysis deacetylate gets ocotillol type ginsenoside under the alkaline condition.
D. step c product oxidation in the presence of oxygenant, or at organic bases, condensing agent exists lower, with carboxylic acid, acyl chlorides, anhydride reaction.
E. steps d is through extraction, and column chromatography obtains general formula (I) compound.
Pharmacological testing proves, (20S, 24R) of the present invention-ocotillol type ginsenoside analog derivative has antibacterial activity, can be for the preparation of bacterial-infection resisting medicine.
The below is the pharmacological experimental data of part of compounds of the present invention.
Laboratory apparatus:
Microwell plate
The trace adjustable pipette
Spectrophotometer
Reagent material:
The LB nutrient solution
DMSO
Streptococcus aureus
Colon bacillus
Experimental technique:
In 96 orifice plates of sterilizing, add LB nutrient solution (every hole 100 μ L).Use B2, C2, the D2 hole contrasts as healthy bacterium, E11, F11, the G11 hole is as blank.With micro-adjustable pipette at B3, C3, add the DMSO of 0.4 μ L in the D3 hole as solvent control, in remaining hole (B4-G10) to add 0.4 μ L concentration be that the compound solution that 50mM is dissolved in DMSO makes it to become the solution that concentration is 200uM (repeating 3 holes); Then add the same day in the fresh growth of LB nutrient solution in the every hole of B2-G10, absorbancy is the bacterium liquid 5 μ L between the 0.6-1.0, and microwell plate is added a cover and sealed to reduce evaporation in the process of hatching with gummed paper, uses
OPTIMA plate reader (BMG LABTECH) is hatched 18h in 37 ℃, and makes 96 orifice plates in the up and down concussion of 7mm distance, and per 10 minutes static and read absorbancy at 600nm.
If bacterium all is killed, then proceed the minimal inhibitory concentration experiment of this medicine under this drug level.Method is: add LB nutrient solution (every hole 100 μ L) in 96 orifice plates of sterilizing.Use B2, C2, the D2 hole contrasts as healthy bacterium, E11, F11, the G11 hole is as blank.At B3, C3 adds the DMSO of 0.4 μ L as solvent control in the D3 hole with micro-adjustable pipette, and adding successively concentration in remaining hole in (B4-G10) from the lower concentration to the high density is the compound liquid (repeating 3 holes) that 50mM is dissolved in DMSO; The concentration of compound in each hole is respectively (... 1.25,2.5,5,10,20,40,80,160,200) and μ MolL
-1Then add the same day in the fresh growth of LB nutrient solution in the every hole of B2-G10, absorbancy is the bacterium liquid 5 μ L between the 0.6-1.0.Microwell plate is added a cover and is sealed to reduce evaporation in the process of hatching with gummed paper, uses
OPTIMA plate reader (BMG LABTECH) is hatched 18h in 37 ℃, and makes 96 orifice plates in the up and down concussion of 7mm distance, and per 10 minutes static and read absorbancy at 600nm, and calculate minimal inhibitory concentration (MIC/mgL
-1).
Experimental result:
The anti-microbial activity (MIC) of Table1. (20S, 24R)-ocotillol type Hydrolizates
Embodiment
The present invention is further elaborated below in conjunction with specific examples, but the present invention is not limited to these embodiment.
Embodiment 1
(20S, 24R)-epoxy dammarane-3 beta, 12 β, 25-triol
20 (S)-protopanoxadiols (500mg, 1.08mmol) are dissolved in the anhydrous pyridine (3mL), add DMAP (20mg, 0.16mmol), the rear slow dropping diacetyl oxide (0.42mL, 4.43mmol) that stirs, stirring at room 12h.Ethyl acetate (20mL) dilution, 10% hydrochloric acid is washed till acidity, washing, the saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=10: 1), get white solid A-1 (508mg, 85%).
With A-1 (208mg obtained above, 0.38mmol) be dissolved in the anhydrous methylene chloride (6mL), cryosel is bathed and is slowly dripped metachloroperbenzoic acid (185mg under the precooling, 75%, 0.16mmol) methylene dichloride (5mL) solution, dropwise and rise to stirring at room reaction 2h after half an hour.Add Virahol (0.1mL), continue to stir after 1 hour, add saturated sodium bicarbonate solution and stir separatory extraction after a hour, organic phase is used saturated sodium thiosulfate solution, water, saturated common salt water washing successively, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=8: 1), get white solid X
1(132mg, 62%).
With X obtained above
1(132mg, 0.24mmol) is dissolved in DMSO (8mL) and H
2Among the O (2mL), add potassium hydroxide (85mg, 1.52mmol), 135 ℃ of stirring reaction 2h.After reaction solution is chilled to room temperature, add an amount of water, a large amount of white solids are separated out, suction filtration, drying, column chromatography (sherwood oil: ethyl acetate=2: 1-1: 1), get compound 1{ (20S, 24R)-epoxy dammarane-3,12, the 25-triol, 66mg} and 2{ (20S, 24S)-epoxy dammarane-3,12, the 25-triol, 50mg}.
MS(ESI)m/z：477.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ3.82-3.87(dd，J＝8.4Hz，6.6Hz，1H)，3.47-3.56(td，J＝10.5Hz，4.8Hz，1H)，3.16-3.22(dd，J＝10.8Hz，5.1Hz，1H)，2.15-2.23(td，J＝10.8Hz，3.6Hz，1H)，1.28(s，3H)，1.27(s，3H)，1.10(s，3H)，0.99(s，3H)，0.97(s，3H)，0.90(s，3H)，0.86(s，3H)，0.78(s，3H)。
Embodiment 2
(20S, 24R)-epoxy dammarane-3 beta, 6 α, 12 β, 25-tetrol
Take 20 (S)-Protopanaxatriols as raw material, implement with reference to (20S, 24R)-epoxy dammarane-3 beta, 12 β, the synthetic method of 25-triol gets white solid (58mg, 48.3%).
MS(ESI)m/z：493.3[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ4.09-4.15(dd，J＝11.0Hz，7.1Hz，1H)，3.84-3.90(dd，J＝10.4Hz，5.1Hz，1H)，3.48-3.57(td，J＝10.2Hz，4.6Hz，1H)，3.15-3.21(dd，J＝11.1Hz，5.0Hz，1H)，2.21-2.29(td，J＝10.6Hz，4.1Hz，1H)，1.32(s，3H)，1.27(s，3H)，1.23(s，3H)，1.10(s，3H)，1.09(s，3H)，0.98(s，3H)，0.94(s，6H)。
Embodiment 3
(20S, 24R)-epoxy dammarane-12 β, 25-glycol-3-ketone
Compound 1 (40mg, 0.08mmol) is dissolved in the anhydrous methylene chloride (3mL), adds PCC (pyridinium chloro-chromate, 36mg, 0.17mmol), stirring at room 3 hours.Decompression desolventizes, acetic acid ethyl dissolution, and extraction, the organic layer washing, the saturated common salt washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=10: 1), get white solid (23mg, 58%).
MS(ESI)m/z：475.3[M+H]
+。
1H?NMR(CDCl
3，500MHz)δ3.84-3.87(dd，J＝8.6Hz，6.0Hz，1H)，3.50-3.55(td，J＝10.5Hz，4.5Hz，1H)，2.48-2.54(m，1H)，2.39-2.45(ddd，J＝11.5Hz，7.5Hz，4.0Hz，1H)，2.18-2.23(td，J＝11.5Hz，3.5Hz，1H)，1.28(s，6H)，1.10(s，3H)，1.07(s，3H)，1.04(s，3H)，1.02(s，3H)，0.96(s，3H)，0.91(s，3H)。
Embodiment 4
(20S, 24R)-epoxy dammarane-12 β, 25-glycol-3-ketoxime
With (20S, 24R)-epoxy dammarane-12 β, 25-glycol-3-ketone (80mg, 0.17mmol) is dissolved in the anhydrous pyridine, adds oxammonium hydrochloride (28mg, 0.39mmol) under the room temperature, and 60 ℃ were reacted three hours.The ethyl acetate dilution, 10% hydrochloric acid is washed till acidity, washing, the saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=1: 1), get white solid (70mg, 85%).
MS(ESI)m/z：490.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ3.82-3.87(m，2H)，3.46-3.55(td，J＝10.3Hz，4.3Hz，1H)，2.94-3.04(m，1H)，2.15-3.33(m，2H)，1.95-2.07(m，2H)，1.34(s，3H)，1.28(s，3H)，1.13(s，3H)，1.10(s，3H)，1.05(s，3H)，1.01(s，3H)，0.95(s，3H)，0.88(s，3H)。
Embodiment 5
(20S, 24R)-epoxy dammarane-3 beta, 25-glycol-12-ketone
Compound 1 (60mg, 0.13mmol) is dissolved in the anhydrous methylene chloride (6mL), adds DMAP (16mg, 0.13mmol), diacetyl oxide (0.04mL, 0.26mmol), stirring at room 24 hours.Decompression desolventizes, acetic acid ethyl dissolution, and extraction, the organic layer washing, the saturated common salt washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=2: 1), get white solid (60mg, 92%).
Above-mentioned white solid (120mg, 0.23mmol) is dissolved in the anhydrous methylene chloride (5mL), adds PCC (pyridinium chloro-chromate, 145mg, 0.69mmol), stirring at room 24 hours.Decompression desolventizes, acetic acid ethyl dissolution, and extraction, the organic layer washing, the saturated common salt washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=8: 1), get white solid (72mg, 60%).
Above-claimed cpd (72mg, 0.14mmol) is dissolved in the methyl alcohol (5mL), adds 0.5mL water and potassium hydroxide (24mg, 0.42mmol), back flow reaction 3h, decompression remove portion methyl alcohol adds suitable quantity of water, white solid is separated out, suction filtration, drying, column chromatography (sherwood oil: ethyl acetate=1: 1), get white solid (60mg, 90%).
MS(ESI)m/z：475.4[M+H]
+。
1H?NMR(CDCl
3，500MHz)δ3.68-3.71(dd，J＝8.5Hz，6.0Hz，1H)，3.17-3.21(dd，J＝11.5Hz，5.0Hz，1H)，2.89-2.91(d，J＝10.0Hz，1H)，2.55-2.59(td，J＝10.5Hz，4.5Hz，1H)，2.19-2.21(m，2H)，1.207(s，3H)，1.198(s，3H)，1.11(s，3H)，1.10(s，3H)，0.99(s，3H)，0.93(s，3H)，0.80(s，3H)，0.76(s，3H)。
Embodiment 6
(20S, 24R)-epoxy dammarane-25-alcohol-3, the 12-diketone
Compound 1 (50mg, 0.10mmol) is dissolved in the anhydrous methylene chloride (5mL), adds PCC (pyridinium chloro-chromate, 74mg, 0.35mmol), stirring at room 24 hours.Decompression desolventizes, acetic acid ethyl dissolution, and extraction, the organic layer washing, the saturated common salt washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=10: 1), get white solid (38mg, 80%).
MS(ESI)m/z：473.4[M+H]
+。
1H?NMR(CDCl
3，500MHz)δ3.68-3.71(dd，J＝10.0Hz，6.5Hz，1H)，2.92-2.94(d，J＝9.5Hz，1H)，2.53-2.60(tdJ＝10.5Hz，4.5Hz，1H)，2.48-2.50(m，1H)，2.39-2.45(ddd，J＝11.5Hz，7.5Hz，4.0Hz，1H)，2.20-2.30(m，2H)，1.26(s，3H)，1.24(s，3H)，1.21(s，3H)，1.11(s，3H)，1.10(s，3H)，1.06(s，3H)，1.03(s，3H)，0.78(s，3H)。
Embodiment 7
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-ethanoyl)-dammarane
Compound 1 (60mg, 0.13mmol) is dissolved in the anhydrous methylene chloride (6mL), adds DMAP (16mg, 0.13mmol), diacetyl oxide (0.04mL, 0.26mmol), stirring at room 24 hours.Decompression desolventizes, acetic acid ethyl dissolution, and extraction, the organic layer washing, the saturated common salt washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=1: 1), get white solid (60mg, 92%).
MS(ESI)m/z：519.3[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ4.45-4.51(dd，J＝9.7Hz，6.4Hz，1H)，3.85-3.90(dd，J＝10.0Hz，5.2Hz，1H)，3.47-3.56(dd，J＝10.2Hz，4.3Hz，1H)，2.09-2.30(m，1H)，2.04(s，3H)，1.27(s，6H)，1.10(s，3H)，0.99(s，3H)，0.97(s，3H)，0.90(s，3H)，0.88(s，3H)，0.86(s，3H)。
Embodiment 8
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-acryl)-dammarane
With vinylformic acid (0.16mL, 0.22mmol), DMAP (20mg, 0.16mmol), DCC (52mg, 0.25mmol) is dissolved in the anhydrous methylene chloride (8mL), add compound 1 (80mg, 0.17mmol), room temperature reaction 24h after half an hour.Decompression desolventizes, acetic acid ethyl dissolution, and extraction, the organic layer washing, the saturated common salt washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=4: 1), get white solid (56mg, 48%).
MS(ESI)m/z：531.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ6.34-6.40(d，J＝17.3Hz，1H)，6.06-6.16(dd，J＝17.3Hz，10.3Hz，1H)，5.78-5.81(d，J＝10.4Hz，1H)，4.51-4.56(dd，J＝10.7Hz，5.2Hz，1H)，3.82-3.87(t，J＝8.0Hz，7.0Hz，1H)，3.48-3.56(td，J＝10.4Hz，5.9Hz，1H)，2.15-2.26(m，1H)，1.27(s，9H)，1.09(s，3H)，0.99(s，3H)，0.90(s，3H)，0.89(s，3H)，0.86(s，3H)。
Embodiment 9
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-{ 3 β-O-(2E, 4E)-hexadiene acyl group }-dammarane
With reference to (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-acryl)-dammarane's synthetic method.Get white solid (50mg, 43%).
MS(ESI)m/z：571.3[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ7.18-7.27(dd，J＝15.4Hz，9.9Hz，1H)，6.08-6.24(m，2H)，5.75-5.80(d，J＝15.4Hz，1H)，4.52-4.58(dd，J＝10.1Hz，5.0Hz，1H)，3.83-3.87(dd，J＝8.5Hz，6.8Hz，1H)，3.48-3.57(td，J＝10.5Hz，5.8Hz，1H)，2.13-2.23(m，1H)，1.28(s，3H)，1.27(s，3H)，1.26(s，3H)，1.10(s，3H)，0.99(s，3H)，0.91(s，3H)，0.90(s，3H)，0.89(s，3H)，0.86(s，3H)。
Embodiment 10
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-capryloyl)-dammarane
With sad (0.025ml, 0.125mmol), DMAP (20mg, 0.16mmol), EDCI (50mg, 0.25mmol) is dissolved in the anhydrous methylene chloride (8mL), add compound 1 (60mg, 0.12mmol), room temperature reaction 24h after half an hour.Decompression desolventizes, acetic acid ethyl dissolution, and extraction, the organic layer washing, the saturated common salt washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=4: 1), get white semisolid (68mg, 90%).
MS(ESI)m/z：603.5[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ4.38-4.43(dd，J＝10.1Hz，5.7Hz，1H)，3.75-3.80(dd，J＝8.6Hz，6.8Hz，1H)，3.40-3.49(td，J＝10.4Hz，4.6Hz，1H)，2.19-2.24(t，J＝7.4Hz，2H)，2.17-2.19(m，1H)，1.29(s，3H)，1.26(s，6H)，1.05(s，3H)，0.98(s，3H)，0.90(s，3H)，0.88(s，3H)，0.84(s，3H)。
Embodiment 11
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-benzoyl)-dammarane
With reference to (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-capryloyl)-dammarane's synthetic method.Get white solid (62mg, 86%).
MS(ESI)m/z：581.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ8.02-8.05(d，J＝7.7Hz，2H)，7.52-7.57(t，J＝7.2Hz，7.0Hz，1H)，7.41-7.46(t，J＝7.5Hz，7.4Hz，2H)，4.69-4.74(dd，J＝10.6Hz，5.5Hz，1H)，3.82-3.87(t，J＝7.5Hz，7.4Hz，1H)，3.49-3.58(td，J＝10.2Hz，4.2Hz，1H)，2.14-2.24(m，1H)，1.27(s，6H)，1.10(s，3H)，1.01(s，6H)，0.92(s，9H)。
Embodiment 12
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(the adjacent cyano group benzoyl of 3 β-O-)-dammarane
With reference to (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-capryloyl)-dammarane's synthetic method gets white solid (40mg, 82%).
MS(ESI)m/z：606.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ8.21-8.24(d，J＝7.6Hz，1H)，7.82-7.867(m，2H)，7.74-7.77(d，J＝8.3Hz，1H)，4.69-4.74(dd，J＝10.6Hz，5.5Hz，1H)，3.81-3.86(t，J＝7.5Hz，7.4Hz，1H)，3.49-3.58(td，J＝10.2Hz，4.2Hz，1H)，2.14-2.23(m，1H)，1.25(s，6H)，1.14(s，3H)，1.02(s，6H)，0.93(s，9H)。
Embodiment 13
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(benzoyl bromide between 3 β-O-)-dammarane
With reference to (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-capryloyl)-dammarane's synthetic method gets white solid (46mg, 85%).
MS(ESI)m/z：659.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ8.21-8.25(m，1H)，7.94-8.01(m，1H)，7.76-7.80(m，1H)，7.43-7.46(m，1H)，4.71-4.77(dd，J＝10.5Hz，4.7Hz，1H)，3.82-3.90(dd，J＝10.1Hz，4.9Hz，1H)，3.51-3.56(td，J＝10.4Hz，5.4Hz，1H)，2.20-2.26(m，1H)，1.25(s，3H)，1.26(s，3H)，1.13(s，3H)，1.04(s，3H)，1.02(s，3H)，0.98(s，3H)，0.96(s，6H)。
Embodiment 14
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-o-hydroxy formyl radical)-dammarane
With reference to (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-capryloyl)-dammarane's synthetic method.Get white solid (50mg, 68%).
MS(ESI)m/z：597.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ7.81-7.84(d，J＝7.9Hz，1H)，7.42-7.47(t，J＝7.1Hz，7.0Hz，1H)，6.98-6.99(d，J＝8.3Hz，1H)，6.85-6.90(t，J＝7.6Hz，7.4Hz，1H)，4.72-4.77(t，J＝9.1Hz，6.7Hz，1H)，3.83-3.88(t，J＝8.4Hz，6.9Hz，1H)，3.49-3.58(td，J＝10.4Hz，4.5Hz，1H)，2.14-2.26(m，1H)，1.28(s，3H)，1.27(s，3H)，1.26(s，3H)，1.10(s，3H)，1.01(s，6H)，0.92(s，6H)。
Embodiment 15
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-3-pyridine formyl radical)-dammarane
With reference to (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-capryloyl)-dammarane's synthetic method.Get white solid (51mg, 70%).
MS(ESI)m/z：582.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ9.22(s，1H)，8.76-8.78(d，J＝3.9Hz，1H)，8.28-8.30(d，J＝7.4Hz，1H)，7.37-7.41(t，J＝7.0Hz，5.4Hz，1H)，δ4.73-4.78(t，J＝9.5Hz，5.7Hz，1H)，3.83-3.88(t，J＝7.5Hz，7.2Hz，1H)，3.49-3.57(td，J＝6.5Hz，4.2Hz，1H)。
Embodiment 16
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-2-furancarbonyl)-dammarane
With reference to (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-capryloyl)-dammarane's synthetic method.Get white solid (48mg, 72%).
MS(ESI)m/z：571.4[M+H]
+.
1H?NMR(CDCl
3，300MHz)δ7.57(s，1H)，7.12-7.13(d，J＝3.4Hz，1H)，6.48-6.50(t，J＝1.7Hz，1.6Hz，1H)，4.67-4.73(t，J＝9.1Hz，6.4Hz，1H)，3.83-3.87(t，J＝8.0Hz，6.6Hz，1H)，3.48-3.57(td，J＝10.3Hz，4.4Hz，1H)，2.14-2.26(m，1H)，1.27(s，6H)，1.26(s，3H)，1.10(s，3H)，1.00(s，3H)，0.95(s，3H)，0.90(s，6H)
Embodiment 17
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-{ 3 β-O-(E)-phenylpropenoyl }-dammarane
Cinnamyl chloride (32mg, 0.19mmol) is dissolved in the anhydrous methylene chloride (5mL), adds 1 triethylamine, add compound 1 (60mg, 0.126mmol), room temperature reaction three hours after ten minutes, reaction solution is successively through 10% hydrochloric acid, water, saturated common salt water washing, anhydrous sodium sulfate drying, filter, concentrated, column chromatography (sherwood oil: ethyl acetate=3: 1), get white solid (58mg, 76%).
MS(ESI)m/z：607.3[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ7.64-7.69(d，J＝16.0Hz，1H)，7.52-7.55(m，2H)，7.37-7.39(m，3H)，6.41-6.47(d，J＝16.0Hz，1H)，4.59-4.65(dd，J＝9.7Hz，5.1Hz，1H)，3.82-3.98(t，J＝8.5Hz，6.7Hz，1H)，3.49-3.56(td，J＝10.0Hz，4.7Hz，1H)，2.10-2.26(m，1H)，1.26(s，3H)。
Embodiment 18
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-(E)-p-nitrophenyl acryl)-dammarane
Reference compound (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-(E)-phenylpropenoyl)-dammarane's synthetic method gets white solid (42mg, 70%).
MS(ESI)m/z：652.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ7.64-7.69(d，J＝16.0Hz，1H)，7.52-7.55(m，2H)，7.37-7.39(m，2H)，6.41-6.47(d，J＝16.0Hz，1H)，4.59-4.65(dd，J＝9.7Hz，5.1Hz，1H)，3.82-3.98(t，J＝8.5Hz，6.7Hz，1H)，3.49-3.56(td，J＝10.0Hz，4.7Hz，1H)，2.10-2.26(m，1H)，1.26(s，3H)。
Embodiment 19
4-{ (20S, 24R)-epoxy-12 β, 25-dihydroxyl dammarane-3 beta-oxygen base }-the 4-ketobutyric acid
Succinic anhydried (32mg, 0.32mmol), DMAP (15mg, 0.12mmol) are dissolved in the anhydrous methylene chloride the rear adding compound 1 (50mg, 0.105mmol) that stirs, heating reflux reaction 12h.Decompression desolventizes, ethyl acetate dilution, and 10% hydrochloric acid successively, water, the saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (methylene dichloride: methyl alcohol=80: 1), get white solid (47mg, 78%).
MS(ESI)m/z：577.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ4.47-4.53(t，J＝8.9Hz，6.9Hz，1H)，3.82-3.87(t，J＝8.0Hz，7.3Hz，1H)，3.49-3.55(dd，J＝10.1Hz，6.3Hz，1H)，2.63-2.67(m，4H)，2.15-2.22(m，1H)，1.29(s，3H)，1.26(s，6H)，1.00(s，3H)，0.98(s，3H)，0.90(s，3H)，0.88(s，3H)，0.84(s，3H)。
Embodiment 20
4-{ (20S, 24R)-epoxy-12 β, 25-dihydroxyl dammarane-3 beta-oxygen base }-4-oxo-2 (E)-alkene butyric acid
With reference to 4-{ (20S, 24R)-epoxy-12 β, 25-dihydroxyl dammarane-3 beta-oxygen base }-synthetic method of 4-ketobutyric acid.Get white solid (26mg, 43%).
MS(ESI)m/z：575.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ6.39-6.44(d，J＝12.8Hz，1H)，6.28-6.32(d，J＝12.8Hz，1H)，4.57-4.62(t，J＝8.3Hz，6.9Hz，1H)，3.76-3.81(t，J＝7.5Hz，7.5Hz，1H)，3.43-3.46(td，J＝10.8Hz，5.6Hz，1H)，2.14-2.26(m，1H)，1.10(s，3H)，0.92(s，3H)，0.81(s，3H)。
Embodiment 21
5-{ (20S, 24R)-epoxy-12 β, 25-dihydroxyl-dammarane-3 beta-oxygen base }-4-oxopentanoie acid
With reference to 4-{ (20S, 24R)-epoxy-12 β, 25-dihydroxyl dammarane-3 beta-oxygen base }-synthetic method of 4-ketobutyric acid.Get white solid (35mg, 56%).
MS(ESI)m/z：591.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ4.46-4.51(t，J＝8.9Hz，6.6Hz，1H)，3.82-3.87(t，J＝7.9Hz，7.2Hz，1H)，3.48-3.56(dd，J＝10.9Hz，4.9Hz，1H)，2.37-2.44(m，4H)，2.15-2.22(m，1H)，1.26(s，6H)，1.10(s，6H)，1.05(s，3H)，0.98(s，3H)，0.90(s，3H)，0.88(s，3H)，0.84(s，3H)。
Embodiment 22
2-{ (20S, 24R)-epoxy-12 β, 25-dihydroxyl dammarane-3 beta-oxygen base }-carbonyl benzoic acid
Tetra hydro Phthalic anhydride (47mg, 0.32mmol), DMAP (15mg, 0.12mmol) are dissolved in the anhydrous pyridine the rear adding compound 1 (50mg, 0.105mmol) that stirs, heating reflux reaction 8h.Decompression desolventizes, the ethyl acetate dilution, and 10% hydrochloric acid is washed till acidity, washing, the saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (methylene dichloride: methyl alcohol=80: 1), get white solid (49mg, 75%).
MS(ESI)m/z：625.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ7.86-7.89(t，J＝5.1Hz，3.6Hz，1H)，7.70-7.73(t，J＝4.9Hz，3.9Hz，1H)，7.54-7.57(t，J＝5.0Hz，3.8Hz，2H)，4.42-4.77(dd，J＝11.3Hz，4.4Hz，1H)，3.33-3.88(t，J＝8.0Hz，7.9Hz，1H)，3.55-3.60(dd，J＝10.1Hz，6.1Hz，1H)，2.18-2.24(t，J＝8.4Hz，8.2Hz，1H)，1.29(s，3H)，1.28(s，3H)，1.12(s，3H)，1.00(s，3H)，0.94(s，3H)，0.91(s，3H)，0.89(s，3H)，0.86(s，3H)。
Embodiment 23
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-glycyl)-dammarane
With Boc-glycine (66mg, 0.38mmol), DMAP (16mg, 0.13mmol), EDCI (35mg, 0.18mmol) be dissolved in the anhydrous methylene chloride (6mL), add compound 1 (60mg, 0.126mmol), room temperature reaction 24h after stirring half an hour.The reaction solution washing, the saturated common salt water washing, drying concentrates to get crude product.This crude product is dissolved in the anhydrous methylene chloride (10ml), adds trifluoracetic acid (1mL, 12.67mmol), room temperature reaction 24h.Slowly add saturated sodium bicarbonate solution, dichloromethane extraction, organic phase is washed successively, the saturated common salt water washing, and anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (methylene dichloride: methyl alcohol=60: 1), get white solid (41mg, 61%).
MS(ESI)m/z：534.4[M+H]
+。
1H?NMR(CDCl
3，500MHz)δ4.53-4.56(dd，J＝10.0Hz，6.9Hz，1H)，3.84-3.87(dd，J＝8.5Hz，6.5Hz，1H)，3.49-3.54(td，J＝10.5Hz，4.5Hz，1H)，2.18-2.23(m，1H)，1.28(s，3H)，1.27(s，3H)，1.10(s，3H)，0.99(s，3H)，0.91(s，3H)，0.89(s，3H)，0.85(s，6H)。
Embodiment 24
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-4-piperidine formyl base)-dammarane
With reference to (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-glycyl)-dammarane's synthetic method.Get white solid (29mg, 39%).
MS(ESI)m/z：588.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ4.48-4.53(t，J＝8.6Hz，7.3Hz，1H)，3.82-3.87(dd，J＝10.2Hz，5.1Hz，1H)，3.51-3.60(td，J＝9.4Hz，6.1Hz，1H)，3.34-3.16(d，J＝11.9Hz，2H)，2.99-3.05(t，J＝9.2Hz，8.8Hz，2H)，2.01-2.21(m，6H)，1.26(s，6H)，1.10(s，3H)，0.99(s，3H)，0.91(s，3H)，0.89(s，3H)，0.86(s，3H)，0.85(s，3H)。
Embodiment 25
(20S, 24R)-epoxy-3 β, 25-dihydroxyl-(12 β-O-ethanoyl)-dammarane
Compound 1 (60mg, 0.13mmol) is dissolved in the anhydrous pyridine (6mL), adds DMAP (16mg, 0.13mmol), diacetyl oxide (0.08mL, 0.52mmol), 80 ℃ were stirred 24 hours.Ethyl acetate (20mL) dilution, 10% hydrochloric acid is washed till acidity, washing, the saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=8: 1), get white solid (60mg, 81%).
Above-claimed cpd (60mg, 0.11mmol) is dissolved in the methyl alcohol (5mL), adds 0.2ml water and potassium hydroxide (12mg, 0.20mmol), 60 ℃ of reaction 12h.Most of methyl alcohol is removed in decompression, the ethyl acetate dilution, and washing, the saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=6: 1), get white solid (46mg, 82%).
MS(ESI)m/z：519.3[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ4.78-4.87(td，J＝10.6Hz，5.3Hz，1H)，3.63-3.68(t，J＝7.1Hz，6.7Hz，1H)，3.17-3.21(dd，J＝11.2Hz，4.2Hz，1H)，2.14-2.33(m，1H)，2.01(s，3H)，1.28(s，3H)，1.26(s，3H)，1.10(s，3H)，1.00(s，3H)，0.98(s，3H)，0.94(s，3H)，0.85(s，3H)，0.77(s，3H).
Embodiment 26
2-{ (20S, 24R)-epoxy-3 β, 25-dihydroxyl-dammarane-12 β-oxygen base }-carbonyl benzoic acid
With (20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-ethanoyl)-dammarane (120mg; 0.23mmol) be dissolved in the 5mL anhydrous pyridine, add DMAP (50mg, 0.41mmol), Tetra hydro Phthalic anhydride (200mg; 1.35mmol), vigorous reflux 30h.The ethyl acetate dilution, 10% hydrochloric acid is washed till acidity, washing, the saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (sherwood oil: ethyl acetate=6: 1), get white solid (70mg, 47%).
Above-claimed cpd (70mg, 0.105mmol) is dissolved in the methyl alcohol (5mL), adds 0.2mL water and potassium hydroxide (12mg, 0.20mmol), 60 ℃ of reaction 12h.Most of methyl alcohol is removed in decompression, the ethyl acetate dilution, and washing, the saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (methylene dichloride: methyl alcohol=30: 1), get white solid (40mg, 61%).
MS(ESI)m/z：625.4[M+H]
+。
1H?NMR(CDCl
3，500MHz)δ7.84-7.86(m，1H)，7.68-7.70(m，1H)，7.56-7.59(m，2H)，5.09-5.15(td，J＝10.5Hz，5.0Hz，1H)，3.55-3.58(t，J＝7.5Hz，6.5Hz，1H)，3.24-3.27(dd，J＝10.5Hz，4.5Hz，1H)，2.11-2.19(m，2H)，1.28(s，3H)，1.09(s，3H)，1.08(s，3H)，1.07(s，3H)，1.03(s，3H)，1.00(s，3H)，0.87(s，3H)，0.76(s，3H)。
Embodiment 27
(20S, 24R)-epoxy-25-hydroxyl-(3 β, 12 β-O-two adjacent carboxylbenzoyls)-dammarane
With (20S, 24R)-epoxy dammarane-3 beta, 12 β, 25-trihydroxy-(120mg, 0.23mmol) is dissolved in the 5mL anhydrous pyridine, adds DMAP (50mg, 0.41mmol), Tetra hydro Phthalic anhydride (445mg, 3.0mmol), vigorous reflux 30h.The ethyl acetate dilution, 10% hydrochloric acid is washed till acidity, washing, the saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (methylene dichloride: methyl alcohol=20: 1), get white solid (70mg, 40%).
MS(ESI)m/z：773.4[M+H]
+。
1H?NMR(CDCl
3，300MHz)δ7.84-7.86(t，J＝5.2Hz，3.5Hz，2H)，7.70-7.72(t，J＝4.8Hz，3.7Hz，2H)，7.56-7.58(t，J＝5.0Hz，3.8Hz，2H)，7.51-7.53(t，J＝5.8Hz，3.6Hz，2H)4.45-4.76(dd，J＝11.3Hz，4.4Hz，1H)，3.33-3.68(t，J＝8.0Hz，7.9Hz，1H)，3.53-3.60(dd，J＝10.1Hz，6.1Hz，1H)，2.16-2.22(t，J＝8.3Hz，8.1Hz，1H)，1.25(s，3H)，1.27(s，3H)，1.15(s，3H)，1.01(s，3H)，0.94(s，3H)，0.91(s，3H)，0.89(s，3H)，0.86(s，3H)。
Embodiment 28
Tablet
Get above-mentioned prescription, be prepared into tablet with ordinary method.
Claims (6)
1. the compound or pharmaceutically acceptable salt thereof of general formula (I):
Wherein:
R
1Be selected from hydroxyl, oxo, hydroxyl oxime generation, acetoxyl group, acryloxy, 2,4-hexadiene acyloxy, hot acyloxy, mesyloxy, tolysulfonyl oxygen base, benzoyloxy, the o-methyl-benzene methanoyl, between toluyl oxygen base, to toluyl oxygen base, the O-methoxy benzoyloxy, the meta-methoxy benzoyloxy, to methoxybenzoyl oxygen base, adjacent chlorobenzoyl oxygen base, the m-chloro benzoyloxy, to chlorobenzoyl oxygen base, adjacent bromobenzene methanoyl, between the bromobenzene methanoyl, to the bromobenzene methanoyl, the o-trifluoromethyl benzoyloxy, the m-trifluoromethyl benzoyloxy, to the trifluoromethyl benzoyloxy, the ortho-nitrophenyl methanoyl, the m-nitro methanoyl, the p-nitrophenyl methanoyl, adjacent cyano group benzoyloxy, between the cyano group benzoyloxy, to the cyano group benzoyloxy, 3-pyridine methanoyl, phenylallene acyl-oxygen base, adjacent chlorobenzene acryloxy, O-methoxy phenylallene acyl-oxygen base, to the bromobenzene acryloxy, the estragole acyloxy, the p-nitrophenyl acryloxy, 2-furoyl oxygen base, 3-carboxyl propionyloxy, 3-carboxyl acryloxy, 4-carboxyl butyryl acyloxy, glycyl oxygen base, 4-piperidine formyl oxygen base, 2-carboxyl benzoyloxy, 2-(2-hydroxybenzoyl) oxygen base, β-D-glucopyanosyl base, β-D-glucopyanosyl base (1-2)-β-D-glucopyanosyl base.
R
2Be selected from hydrogen, hydroxyl, β-D-glucopyanosyl base, α-L-rhamnopyranosyl (1-2)-β-D-glucopyranosyl.
R
3Be selected from hydroxyl, oxo, acetoxyl group, 2-carboxyl benzoyloxy.
2. the compound or pharmaceutically acceptable salt thereof of claim 1, wherein R
1Representation hydroxy, hydroxyl oxime generation, m-chloro benzoyloxy, a bromobenzene methanoyl, o-trifluoromethyl benzoyloxy, p-nitrophenyl methanoyl, adjacent cyano group benzoyloxy, 3-carboxyl propionyloxy, 3-carboxyl acryloxy, 4-carboxyl butyryl acyloxy, glycyl oxygen base, 4-piperidine formyl oxygen base, 2-carboxyl benzoyloxy, phenylallene acyl-oxygen base, p-nitrophenyl acryloxy.
R
2Represent H.
R
3Representation hydroxy, 2-carboxyl benzoyloxy.
3. the compound or pharmaceutically acceptable salt thereof of claim 2, wherein R
1Representation hydroxy, 3-carboxyl acryloxy, 3-carboxyl propionyloxy, 4-carboxyl butyryl acyloxy, glycyl oxygen base, 4-piperidine formyl oxygen base, 2-carboxyl benzoyloxy, adjacent cyano group benzoyloxy, a bromobenzene methanoyl, p-nitrophenyl acryloxy.
R
2Represent H.
R
3Be selected from hydroxyl, 2-carboxyl benzoyloxy.
4. the compound or pharmaceutically acceptable salt thereof of claim 3 wherein has:
4-[(20S, 24R)-epoxy-12 β, 25-dihydroxyl-dammarane-3 beta-oxygen base]-the 4-oxo-butynic acid;
4-[(20S, 24R)-epoxy-12 β, 25-dihydroxyl-dammarane-3 beta-oxygen base]-4-oxo-2 (E)-alkene-butyric acid;
5-[(20S, 24R)-epoxy-12 β, 25-dihydroxyl-dammarane-3 beta-oxygen base]-4-oxo-valeric acid;
2-[(20S, 24R)-epoxy-12 β, 25-dihydroxyl-dammarane-3 beta-oxygen base]-carbonyl-phenylformic acid;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-glycyl)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(3 β-O-4-piperidine formyl base)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(the adjacent cyano group benzoyl of 3 β-O-)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-(benzoyl bromide between 3 β-O-)-dammarane;
(20S, 24R)-epoxy-12 β, 25-dihydroxyl-[3 β-O-(E)-p-nitrophenyl acryl]-dammarane;
2-[(20S, 24R)-epoxy-3 β, 25-dihydroxyl-dammarane-12 β-oxygen base]-carbonyl-phenylformic acid;
(20S, 24R)-epoxy-25-hydroxyl-(3 β, 12 β-O-two adjacent carboxylbenzoyls)-dammarane.
5. the compound of claim 1 or its pharmacy acceptable salt are for the preparation of medicine and pharmaceutically acceptable carrier for the treatment of bacterial infective diseases.
6. the purposes of claim 5, wherein bacterial infective diseases is upper respiratory tract infection, urinary tract infection enteritis, diarrhoea and the septicemia etc. that gram-positive microorganism and gram positive bacterial infection cause.
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