CN102659895A - Steroid alkaloid hydrochloride, its preparation method and application - Google Patents
Steroid alkaloid hydrochloride, its preparation method and application Download PDFInfo
- Publication number
- CN102659895A CN102659895A CN2012101092270A CN201210109227A CN102659895A CN 102659895 A CN102659895 A CN 102659895A CN 2012101092270 A CN2012101092270 A CN 2012101092270A CN 201210109227 A CN201210109227 A CN 201210109227A CN 102659895 A CN102659895 A CN 102659895A
- Authority
- CN
- China
- Prior art keywords
- formula
- compound shown
- reduction
- preparation
- alkaloid hydrochloride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a steroid alkaloid hydrochloride of formula 1 or 2, its preparation method and application. The preparation method comprises the following main steps: letting pregnadienolone acetate of formula 3 as a raw material successively be subject to epoxidation with hydrogen peroxide, protection with tert-butyl dimethyl chloro-silicon hydroxy, reduction with hydrazine hydrate, manganese dioxide alcohol oxidation, and Michael addition with nitromethane to obtain an intermediate of formula 4, letting the intermediate of formula 4 be subject to reduction with sodium borohydride and reduction with zinc powder and hydrochloric acid to obtain a target compound, or letting the intermediate of formula 4 be subject to reduction with zinc powder and acetic acid, reduction with sodium borohydride, deprotection with diluted hydrochloric acid and salt formation to obtain the target compound. The steroid alkaloid hydrochloride has a prospect of being developed into anti-tumor drugs.
Description
Technical field
The present invention relates to a kind of tetrahydroisoquinoline alkaloid hydrochloride.
Background technology
Many natural phant steroidals have obvious anti-tumor activity.Black nightshade is a kind of herbal medicine, is widely used in multiple solid tumor, dermatoma and white blood disease such as treatment liver cancer, lung cancer, mammary cancer at home and abroad.Solamargine, solasonine and solanine are the main active ingredient in the black nightshade, and they are to be the trisaccharide steroidal glycosides vegeto-alkali of aglycon with solasodine or Solanidine.
In recent years, the anti-tumor activity about solamargine and solanine has many research reports.Simultaneously, solasodine and solanine are carried out structural modification, obtain to have the novel tetrahydroisoquinoline alkaloid compounds of anti-tumor activity, enjoy ability technician's concern.
Summary of the invention
Contriver of the present invention modifies the structure of solasodine and solanine, has obtained the novel tetrahydroisoquinoline alkaloid hydrochloride of a class formation.Show through anti tumor activity in vitro test (mtt assay): the prepared tetrahydroisoquinoline alkaloid hydrochloride of the present invention has anti-tumor activity, possesses the prospect that is developed to new type antineoplastic medicine.
One object of the present invention is, a kind of tetrahydroisoquinoline alkaloid hydrochloride is provided, and described tetrahydroisoquinoline alkaloid hydrochloride is a compound shown in formula 1 or the formula 2:
Another object of the present invention is, a kind of method for preparing above-mentioned tetrahydroisoquinoline alkaloid hydrochloride is provided, and the key step of said method is: with pregnant steroid diene alcohol ketone acetic ester (compound shown in the formula 3) is raw material; Through the ydrogen peroxide 50 epoxidation, tertiary butyl dimethyl-silicon chlorine hydroxyl protection is used hydrazine hydrate reduction successively; The oxidation of Manganse Dioxide alcohol; Nitromethane 99Min. Michael addition obtains midbody 3 β-tertiary butyl dimethyl Si base-20 (S)-22-nitro-pregnant steroid-5-alkene-16-ketone (compound shown in the formula 4), by compound shown in the formula 4 through sodium borohydride reduction; The reduction of zinc powder hydrochloric acid obtains target compound (compound shown in the formula 1); Through the reduction of zinc powder acetic acid, sodium borohydride reduction, Hydrogen chloride deprotection and salify obtain target compound (compound shown in the formula 2) by compound shown in the formula 4.
Further object of the present invention is, a kind of purposes of above-mentioned tetrahydroisoquinoline alkaloid hydrochloride is provided, i.e. its application in the preparation antitumor drug.
Embodiment
The method for preparing compound shown in formula 1 or the formula 2 provided by the present invention, its synthesis strategy is following:
The present invention passes through mtt assay; With the positive reference substance of doxorubicin, compound shown in test formula 1 or the formula 2 is to the anti-tumor activity of five kinds of tumor cell line: A549 (human lung carcinoma cell), Colo205 (people's colon-cancer cell), MDA-MB-435 (human breast cancer cell), QGY7703 (human liver cancer cell) and HL-60 (human leukemia cell).Test result shows: compound shown in the formula 1 is to Colo205, MDA-MB-231, the IC of QGY7703 and HL-60
50Value is 6.5-10.7 μ g/mL; Compound is to the IC of HL-60 shown in the formula 2
50Value is 1.04 μ g/mL.
In addition, the method for preparing formula 1 and compound shown in the formula 2 provided by the invention, its have the reaction conditions gentleness, easy and simple to handle, the stereochemistry selectivity is good, and yield than advantages such as height.
Through specific embodiment the present invention is done further elaboration below, said room temperature is 20 ℃～30 ℃ in the following example.
Embodiment 1
The preparation of compound shown in the formula 1 and 2:
(1) preparation of compound shown in the formula 5
In the 1000mL round-bottomed flask, add 30g compound (3), 500mL methyl alcohol, reaction solution are muddy shape, and ice bath stirs down, keeps system temperature not to be higher than 15 ℃, adds the 40mL 4mol/L NaOH aqueous solution successively and (6.4gNaOH is dissolved in 40mL H
2Among the O), 120mL 30% ydrogen peroxide 50, room temperature reaction 8h (it is complete that TLC detects raw material reaction); Reaction solution is poured in the 1000mL water, hold over night, decompress filter with filtration cakes torrefaction, obtains white solid 26.7g (compound shown in the formula 5), and yield is 96.0%, and fusing point is 176-178 ℃.
(2) preparation of compound shown in the formula 6
In the 1000mL round-bottomed flask, compound shown in the 26.7g formula 5 is dissolved in 500mL CH
2Cl
2In, stir down, add 14.0g TBSCl (clarification) and 13.0g imidazoles (becoming muddy) successively, room temperature reaction 10h (TLC detects raw material and disappears); With the reaction solution suction filtration, remove insoluble dope, mother liquor concentrates, and with 95% alcohol-water recrystallization, separates out crystal, and suction filtration obtains white paillette shape solid 35.0g (compound shown in the formula 6), and yield is 97%, and fusing point is 124-125 ℃.
(3) preparation of compound shown in the formula 7
In the 500mL there-necked flask, add raw material (compound shown in the formula 7) 30.0g and 400mL ethanol, reaction unit places oil bath, and reflux when reaction solution is clarified, adds the 4.5gNaOH solid; After treating that the NaOH solid dissolves fully, slowly drip Hydrazine Hydrate 80 10.0mL with the constant voltage drop-burette, about 15-30min, the control flow velocity makes and do not separate out solid in the reaction solution is good, reaction 6h (TLC detects raw material and disappears); With reaction solution, with the 15mL Glacial acetic acid min. 99.5 pH of reaction solution is transferred to neutrality, slowly drip 25mL water, separate out solid until reaction solution, stop to add water; Solid is separated out in the reaction solution cooling, the room temperature hold over night, and solid is separated out fully, suction filtration, drying obtains faint yellow solid 27.3g (compound shown in the formula 7), and the bullion yield is 90.1%.
1H-NMR(CDCl
3)δ：5.61(1H，q，J＝7.2Hz，H-20)，5.32(1H，m，H-6)，4.44(1H，d，J＝3.6Hz，H-16)，3.43(1H，m，H-3)，1.74(3H，d，J＝7.2Hz，CH
3-21)，0.95(3H，s，CH
3-19)，0.89(9H，s，t-Bu-Si)，0.83(3H，s，CH
3-18)，0.06(6H，s，CH
3-Si)；
13C-NMR(CDCl
3)δ：155.3(C-17)，141.5(C-5)，120.9(C-6)，119.6(C-20)，74.4(C-16)，72.5(C-3)，52.7(C-14)，50.1(C-9)，44.1(C-12)，42.8(C-4)，37.2(C-1)，37.2(C-13)，36.6(C-10)，35.1(C-15)，32.0(C-7)，31.6(C-2)，30.8(C-9)，25.9(t-Bu-Si)，21.0(C-11)，19.3(C-19)，18.2(Me-Si)，17.2(C-18)，13.2(C-21)。
(4) preparation of compound shown in the formula 8
In the 500mL there-necked flask, pure article 12.0g is dissolved in 250mL CH with raw material (compound shown in the formula 8)
2Cl
2In, every 6g activity MnO that pulverizes that adds at a distance from 1.5h
2, mechanical stirring, reaction 8h (the TCL detection reaction is complete); With the reaction solution suction filtration, soak and washing leaching cake with 3 * 100mL methylene dichloride, merge mother liquor, concentrating under reduced pressure; Obtain bullion 10.8g, 90.0% usefulness, 95% alcohol-water recrystallization obtains white solid 9.7g (compound shown in the formula 8); Yield is 80.8%, and fusing point is 168-169 ℃, mass spectrum m/z [M
++ 1] 429.4.
1H-NMR(CDCl
3)δ：6.52(1H，q，J＝7.4Hz，H-20)，5.34(1H，m，H-6)，3.51(1H，m，H-3)，1.88(3H，d，J＝7.2Hz，CH
3-21)，1.09(3H，s，CH
3-19)，1.06(3H，s，CH
3-18)；
13C-NMR(CDCl
3)δ：206.3(C-16)，147.8(C-17)，141.7(C-5)，129.2(C-20)，120.5(C-6)，72.5(C-3)，50.3(C-14)，49.9(C-9)，44.1(C-12)，42.8(C-4)，38.0(C-1)，37.7(C-13)，36.7(C-10)，36.1(C-15)，32.0(C-7)，31.6(C-2)，30.6(C-9)，20.7(C-11)，19.4(C-19)，17.3(C-18)，13.2(C-21)。
(5) preparation of compound shown in the formula 4
In the 500mL there-necked flask, sodium methylate 4.03g is dissolved in the 100mL absolute ethyl alcohol, heat temperature raising slowly drips 3.65mL Nitromethane 99Min., magnetic agitation to 45-55 ℃ with the constant voltage drop-burette; Take by weighing raw material (compound shown in the formula 8) 8.0g, add the absolute ethyl alcohol of 100mL, be mixed with turbid solution, this turbid solution is added in the reaction solution (about 30min) with dropper, reaction 5h (TLC tracks to and reacts completely); With 10% dilute acetic acid reaction solution pH is transferred to 7～8, again reaction solution is poured in the 400mL water of stirring, separate out solid; Suction filtration, drying is with 95% alcohol-water recrystallization; Obtain solid 7.2g, yield is 78.8%, uses PE: EA=8: 1 (v/v) developping agent; Silicagel column separates, and obtains compound shown in the formula 4, and fusing point is 171-173 ℃.
1H-NMR(CDCl
3)δ：5.32(1H，d，6-H)，5.02(1H，dd，J＝12.0，3.7Hz，Ha-22)，4.57(H，dd，J＝12.0，8.4Hz，Hb-22)，3.50(1H，m，H-3)，2.52(1H，m，H-20)，1.12(3H，d，J＝6.7Hz，CH
3-21)，1.08(3H，s，CH
3-19)，0.83(3H，s，CH
3-18)；
13C-NMR(CDCl
3)δ：217.7(C-16)，141.8(C-5)，120.2(C-6)，80.1(C-22)，72.4(C-3)，63.7(C-17)，50.6(C-14)，49.7(C-9)，42.9(C-12)，42.7(C-4)，38.6(C-13)，37.0(C-1)，36.6(C-15)，31.9(C-20)，31.7(C-7)，30.9(C-8)，30.7(C-2)，20.5(C-11)，19.4(C-19)，17.2(C-18)，13.0(C-21)。
Mass spectrum m/z [M
+-1] 488.3.
(6) preparation of compound shown in the formula 9
6.0g is dissolved in the 150mL absolute ethyl alcohol with raw material (compound shown in the formula 4), adds the 0.8g Peng Qinghuana under the room temperature in batches, and TLC trace point plate behind the stirring 10h disappears until raw material; With 10% dilute acetic acid reaction solution is transferred pH to 7-8, then reaction solution is slowly poured in the water, separate out solid, suction filtration, filter cake obtain white solid 5.3g (compound shown in the formula 9) with 95% alcohol-water recrystallization, yield 88.3%, fusing point 173-175 ℃.
1H-NMR(CDCl
3)δ：5.31(1H，d，H-6)，4.70(1H，dd，J＝11.2，3.6Hz，Ha-22)，4.38(1H，dd，J＝11.2，5.2Hz，Hb-22)，4.35(1H，m，H-16)，3.48(1H，m，H-3)，2.70(1H，m，H-20)，1.13(3H，d，J＝7.6Hz，CH
3-21)，1.01(3H，s，CH
3-19)，0.94(3H，s，CH
3-18)，0.89(9H，s，t-Bu-Si)，0.06(6H，s，CH
3-Si)；
13C-NMR(CDCl
3)δ：141.7(C-5)，120.6(C-6)，81.8(C-22)，72.5(C-16)，71.6(C-3)，57.4(C-17)，54.3(C-14)，50.0(C-9)，42.7(C-12)，42.5(C-4)，39.6(C-13)，37.9(C-1)，37.2(C-10)，36.5(C-15)，32.0(C-20)，31.7(C-7)，31.4(C-8)，30.6(C-2)，25.9(t-Bu-Si)，20.6(C-11)，19.4(C-19)，18.2(CH
3-Si)，16.9(C-18)，13.1(C-21)。
(7) preparation of compound shown in the formula 1
300mg is dissolved in the 30mL absolute ethyl alcohol with raw material (compound shown in the formula 9), and stirring at room drips 1N hydrochloric acid 5mL, adds the 400mg zinc powder in batches, reaction 5h, and the TLC detection reaction is complete; With the reaction solution suction filtration, remove zinc powder, the mother liquor concentrating under reduced pressure is used CH
2Cl
2: CH
3OH=5: 1 (V/V) crosses post, obtains white solid 164mg (compound shown in the formula 1), yield 54.7%, fusing point＞300 ℃.
1H-NMR(d-DMSO)δ：7.8(w，NH
2.HCl)，5.26(1H，m，H-6)，4.62(1H，d，OH)，4.14(1H，m，H-16)，3.25(1H，m，H-3)，3.05(1H，dd，J＝12.4，2.8Hz，H-22a)，2.51(1H，m，H-22b)1.01(3H，d，J＝6.8Hz，CH
3-21)，0.94(3H，s，CH
3-19)，0.84(3H，s，CH
3-18)；
13C-NMR(d-DMSO)δ：141.8(C-5)，120.8(C-6)，70.4(C-16)，69.8(C-3)，58.3(C-17)，54.3(C-14)，50.1(C-9)，44.4(C-22)，42.7(C-12)，42.3(C-4)，39.5(C-13)，37.4(C-1)，37.3(C-10)，36.5(C-15)，31.9(C-20)，31.8(C-7)，31.6(C-8)，29.5(C-2)，20.7(C-11)，19.6(C-19)，16.8(C-18)，13.2(C-21)。
(8) preparation of compound shown in the formula 10
Raw material (compound shown in the formula 4) 200mg is dissolved in the 40mL absolute ethyl alcohol, drips HOAc0.6mL under the room temperature, adds the 0.5g zinc powder then in batches, reaction 10h (TLC point plate, raw material completely dissolve); Suction filtration is removed the excessive zinc powder and the white solid of generation, and mother liquor is put for a long time and is prone to redden; Vacuum rotary steam is removed ethanol, obtains thick solid; Extract three times with ETHYLE ACETATE/water, merge organic phase, use saturated NaHCO
3The aqueous solution, the saturated NaCl aqueous solution is respectively washed once MgSO
4Drying concentrates, and with 95% alcohol-water recrystallization, obtains faint yellow solid 150mg (compound shown in the formula 10), and yield is 83.3%, fusing point 167-169 ℃.
1H-NMR(CDCl
3)δ：5.34(1H，m，H-6)，4.17(1H，dd，Ha-22)，3.5(1H，dd，Hb-22)，3.48(1H，m，H-3)，1.10(3H，d，J＝4.8Hz，CH
3-21)，1.05(3H，s，CH
3-19)，0.91(9H，s，t-Bu-Si)，0.71(3H，s，CH
3-18)，0.08(6H，s，CH
3-Si)；
13C-NMR(CDCl3)δ：190.3(C-16)，141.7(C-5)，120.6(C-6)，73.4(C-22)，72.5(C-3)，72.2(C-17)，57.6(C-14)，50.2(C-9)，42.8(C-4)，39.3(C-13)，38.5(C-12)，37.8(C-1)，37.3(C-10)，35.2(C-20)，32.5(C-7)，32.1(C-8)，32.0(C-15)，28.1(C-2)，21.3(C-11)，19.4(C-19)，18.2(C-21)，13.7(C-18)。
(9) preparation of compound shown in the formula 11
100mg is dissolved in the 12mL absolute ethyl alcohol with raw material (compound shown in the formula 10), and ice bath adds 40mg NaBH4 down, can rise to room temperature reaction naturally, TLC point plate behind the 30min, raw material completely dissolve; Reaction solution is poured in the water, separated out solid, suction filtration, filter cake are used 95% alcohol-water recrystallization again, obtain white solid 90mg (compound shown in the formula 11), and yield 89.8%, fusing point are 213-215 ℃.
1H-NMR(CDCl
3)δ：5.34(1H，m，H-6)，3.68(1H，m，H-16)，3.50(1H，m，H-3)，3.30(1H，dd，J＝10.8，6.8Hz，H-22a)，2.52(1H，dd，J＝10.4，8.4Hz，H-22b)，1.03(3H，s，CH
3-19)，1.02(3H，d，J＝6.8Hz，CH
3-21)，0.91(9H，s，t-Bu-Si)，0.82(3H，s，CH
3-18)，0.08(6H，s，CH
3-Si)；
13C-NMR(CDCl
3)δ：141.6(C-5)，120.9(C-6)，72.6(C-3)，64.3(C-16)，64.1(C-17)，58.5(C-22)，57.4(C-14)，50.2(C-9)，42.8(C-12)，40.8(C-4)，39.8(C-13)，37.4(C-1)，36.7(C-10)，33.4(C-20)，33.3(C-7)，32.2(C-15)，32.1(C-8)，31.4(C-2)，25.0(t-Bu-Si)，20.8(C-11)，19.9(CH
3-Si)，19.4(C-19)，18.3(C-18)，16.4(C-21)。
(10) preparation of compound shown in the formula 2
100mg is dissolved in 15mL CH with raw material (compound shown in the formula 11)
2Cl
2In, under ice bath, drip 1mL1%HCl then, can rise to room temperature naturally and continue reaction 2h, TLC point plate is followed the tracks of, and reacts completely; Reaction solution is obtained CH with methylene dichloride/water extraction
2Cl
2Phase is used anhydrous Na SO
4Drying, concentrating under reduced pressure with 95% alcohol-water recrystallization, obtains white solid 89g (compound shown in the formula 2), and yield is 89%, and fusing point is 289-292 ℃, mass spectrum m/z [M
+-1] 328.3.
1H-NMR(CDCl
3)δ：9.8(1H，br，H-Cl)，9.5(1H，br，H-N)，5.33(1H，m，H-6)，4.11(1H，m，H-O)，3.63(1H，m，H-16)，3.53(1H，m，H-3)，2.93(1H，m，H-22a)，2.49(1H，m，H-22b)，1.13(3H，d，J＝6.8Hz，CH
3-21)，1.03(3H，s，CH
3-19)，0.97(3H，s，CH
3-18)；
13C-NMR(CDCl
3)δ：140.9(C-5)，120.9(C-6)，71.6(C-3)，62.9(C-16)，62.3(C-17)，57.6(C-22)，55.5(C-14)，49.8(C-9)，42.3(C-12)，41.3(C-4)，39.2(C-13)，37.2(C-1)，36.6(C-10)，31.9(C-20)，31.8(C-7)，31.6(C-15)，30.9(C-8)，30.1(C-2)，20.6(C-11)，19.3(C-19)，19.1(C-18)，15.5(C-21)。
Embodiment 2
Formula 1 and the test of antitumor activity of compound shown in the formula 2 (external)
Through mtt assay,, estimate the anti-tumor activity to tumor cell line of new compound with the positive reference substance of doxorubicin.Specifically comprise the steps:
(1) five kind of tumor cell line: A549 (human lung carcinoma cell), Colo205 (people's colon-cancer cell), MDA-MB-435 (human breast cancer cell), QGY7703 (human liver cancer cell) and HL-60 (human leukemia cell), by Shanghai Institute of Pharmaceutical Industry's Pharmacology Lab frozen with go down to posterity.
(2) given the test agent preparation: after DMSO (Merck) dissolving, add solution or uniform suspension that PBS (-) is made into 1000 μ g/ml, then with PBS (-) dilution that contains DMSO.
(3) the two anti-experimental techniques of nutrient solution: RPMI1640+15%NBS+.
(4) experimental technique: mtt assay.It is 4-5 * 10 that the every hole of 96 orifice plates adds 100 μ L concentration
4The cell suspension of individual/mL places 37 ℃, 5%CO
2In the incubator.Behind the 24h, add sample liquid, two multiple holes are established in 10 μ L/ holes, and 37 ℃, 5%CO
2Effect 72h.Every hole adds the MTT solution of 20 μ L 5mg/mL, adds lysate behind the effect 4h, and put in the incubator in 100 μ l/ holes, and 570nm OD value is surveyed with the full-automatic ELIASA of MK-2 in the dissolving back.
(5) experimental result is seen table 1 (formula 1 and the in-vitro multiplication restraining effect (IC of compound shown in the formula 2 to five kinds of tumour cells of human body
50, μ g/mL)
a).
Table 1
#Solasodine is a solasodine
Can be known by table 1: formula 1 has the good in-vitro anti-tumor activity with compound shown in the formula 2 to five kinds of tumor cell lines that tried, and possesses the prospect of researching and developing into the antitumor action medicine.
Claims (4)
1. a tetrahydroisoquinoline alkaloid hydrochloride is characterized in that, described tetrahydroisoquinoline alkaloid hydrochloride is a compound shown in formula 1 or the formula 2:
。
2. a method for preparing the described tetrahydroisoquinoline alkaloid hydrochloride of claim 1 is characterized in that, the key step of said method is: with compound shown in the formula 3 is raw material; Through the ydrogen peroxide 50 epoxidation, tertiary butyl dimethyl-silicon chlorine hydroxyl protection is used hydrazine hydrate reduction successively; The oxidation of Manganse Dioxide alcohol, Nitromethane 99Min. Michael addition obtains compound shown in the midbody formula 4; Through sodium borohydride reduction, the reduction of zinc powder hydrochloric acid obtains compound shown in the formula 1 by compound shown in the formula 4, or
Reduce through zinc powder acetic acid by compound shown in the formula 4, sodium borohydride reduction, Hydrogen chloride deprotection and salify obtain compound shown in the formula 2,
3. the application of tetrahydroisoquinoline alkaloid hydrochloride as claimed in claim 1 in the preparation antitumor drug.
4. application as claimed in claim 3 is characterized in that wherein said tumour comprises lung cancer, intestinal cancer, mammary cancer, liver cancer and white blood disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101092270A CN102659895A (en) | 2012-04-13 | 2012-04-13 | Steroid alkaloid hydrochloride, its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101092270A CN102659895A (en) | 2012-04-13 | 2012-04-13 | Steroid alkaloid hydrochloride, its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102659895A true CN102659895A (en) | 2012-09-12 |
Family
ID=46769503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101092270A Pending CN102659895A (en) | 2012-04-13 | 2012-04-13 | Steroid alkaloid hydrochloride, its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102659895A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113968887A (en) * | 2021-11-15 | 2022-01-25 | 湖南科瑞生物制药股份有限公司 | Preparation method of archaeolsterone intermediate under mild condition |
-
2012
- 2012-04-13 CN CN2012101092270A patent/CN102659895A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113968887A (en) * | 2021-11-15 | 2022-01-25 | 湖南科瑞生物制药股份有限公司 | Preparation method of archaeolsterone intermediate under mild condition |
| CN113968887B (en) * | 2021-11-15 | 2022-10-11 | 湖南科瑞生物制药股份有限公司 | Preparation method of archaeolsterone intermediate under mild condition |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9321804B2 (en) | Synthesis and use of anti-tumor drug LQC-Y | |
| CN100384830C (en) | Derivative of cyclo membranousol kind and application thereof | |
| WO2013000286A1 (en) | Bufogenin derivatives, preparation methods, compositions containing such derivatives and uses thereof | |
| CN102127142B (en) | Ilicis routundae cortex derivants and application thereof in preparing medicament capable of resisting tumors | |
| CN102002051A (en) | ent-6,7-open-cycle kaurene type rubescensine A derivative with anti-tumor activity and preparation method and use thereof | |
| CN103804312A (en) | Nitrogen heterocyclic compounds as well as preparation method and application thereof | |
| US8299125B2 (en) | Water-soluble triterpenephenol compounds having antitumor activity and the preparation thereof | |
| CN101565446B (en) | Veratramine degradation product veratrum fluorene aldehyde and the derivatives thereof, as well as the preparation and application thereof | |
| CN103880910A (en) | Preparation method and application of cycloastragenol | |
| CN105294676A (en) | Berberine double salt and preparation method and application thereof | |
| CN102898433B (en) | Tetrandrine gallate and drug composition, preparation method and applications thereof | |
| CN103288913A (en) | Novel compound, pharmaceutical compositions thereof as well as preparation methods thereof and use of novel compound and pharmaceutical compositions | |
| CN102391352B (en) | Amino acid derivatives of rotundic acid and application of derivatives in preparation of antitumor medicines | |
| CN105859823A (en) | Application of ilicis routundae cortex acid ester derivatives in preparation of anti-tumor drugs | |
| CN102659895A (en) | Steroid alkaloid hydrochloride, its preparation method and application | |
| CN104188978B (en) | The application in preparation treatment or preventing renal fibrosis medicine of O-(nafoxidine base) ethyl derivative of Cleistanone | |
| CN105820206B (en) | 22 drop beans steroid benzimidazole compounds and its preparation method and application | |
| CN104003968A (en) | Natural product 3-prenyl Iuteolin analogue (I)/(II), preparation method of natural product 3-prenyl Iuteolin analogue (I)/(II), and application of natural product 3-prenyl Iuteolin analogue (I)/(II) | |
| CN105859821A (en) | 22-nor-stigmasta thiosemicarbazone compound and preparing method and application thereof | |
| CN109705189B (en) | Triterpene derivative with structure shown in formula I, preparation method and application thereof | |
| CN101367786A (en) | Preparation method of genistein nitric oxide donor type derivant and uses thereof | |
| CN103910741B (en) | Bisbenzylisoquinolincompounds trimethyl-glycine and preparation method thereof and the application in antitumor drug preparation | |
| CN110804084B (en) | Quaternary phosphonium salt diosgenin derivative and synthesis method and application thereof | |
| CN105712994A (en) | Imidazolone-morphinan as well as preparation method and application thereof | |
| CN103254266B (en) | Steroidal zinc metal complexes and preparation method thereof and the application in the anti-gastric cancer medicament of preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120912 |