CN1341603A - Synthesis method of pregnen ketoalcohol compound - Google Patents
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- CN1341603A CN1341603A CN 01113196 CN01113196A CN1341603A CN 1341603 A CN1341603 A CN 1341603A CN 01113196 CN01113196 CN 01113196 CN 01113196 A CN01113196 A CN 01113196A CN 1341603 A CN1341603 A CN 1341603A
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Abstract
In the organic solvent it uses hydrogen perioxide to oxidate psudosapogenin to obtain pregnene keto-alcohol and 4-methyl-delta-butyrolactone. The obtained pregnene keto-alcohol is a key precursor for synthesizing steroid medicine. The 4-methyl-delta-butyrolactone can be used for synthesizing chiral methyl contained compounds of chiral liquid crystal and insect pheromone, etc. Said invented method is moderate is condition, low in cost, has no pollution and its reaction yield is equal to or greater than that of chrome-anhydride oxidation method.
Description
The present invention relates to the synthetic method of a kind of new NSC 37741 compound, promptly in organic solvent, use the false steroid sapogenines (Psudosapogenin) of catalytic oxidation of hydrogen peroxide, obtain NSC 37741 and 3-methyl-δ-butyrolactone.
In state-owned abundant steroid sapogenines resource, as diosgenin, sisalagenin, zhimusaponin unit, luxuriant numb sapogenin etc., they are basic raw materials of making various steroid drugss.Utilize steroid sapogenines synthesizing steroid medicine, at first need steroid sapogenin degradation is become the NSC 37741 compound.Up to now, the main method that adopts on chemical laboratory and the industrial production is still the degradation method (J.Am.Chem.Soc.1947,69,2167) that chemist Marker provides.Promptly in diacetyl oxide and acetate, pressurize, high temperature (more than 200 ℃) cracking steroid sapogenines becomes corresponding false steroid sapogenines, provides corresponding NSC 37741 through chromic anhydride oxidation and elimination reaction again.Three step total yields are approximately 60%.With the sisalagenin is example, and reaction formula is as follows:
Though after this this degradation method still fails to change the shortcoming that this method has through updating (Micovic I.V.Synthesis, 1990,591).That is, that fails to remove from office degradation process removes the chromic anhydride oxidizing reaction, and that is to say: the problem of environmental pollution in the steroid sapogenin degradation process still fails to solve.For this reason, the inventor launched the steroid sapogenines resource rational utilization is studied from 1991.Provide after deliberation: by the oxidation of organic peroxide acid to steroid sapogenines, the method for the synthetic NSC 37741 peer-to-peer-pregnen alcohol of basic hydrolysis (Chinese patent, CN96116304.6).Two step total yields can reach more than 90%.With the sisalagenin is example, and reaction formula is as follows:
This contriver also study provided direct degradation of steroid sapogenin and become the method for corresponding steroidal-22-carboxylic acid-16-alcoholic lactone (Chinese patent, CN00127974.2):
In the method for the degradation of steroid sapogenin that has provided, they have realized replacing chromic anhydride degradation of steroid sapogenin with hydrogen peroxide, but resulting degraded product can't be directly used in the synthetic of steroid drugs.For the real problem of environmental pollution that solves the steroid sapogenin degradation process, further how research uses the method for pregnen alcohol and steroidal-22-carboxylic acid-16-alcoholic lactone synthesizing steroid medicine, or replaces chromic anhydride degradation of steroid sapogenin to become corresponding NSC 37741 with hydrogen peroxide.In view of NSC 37741 as steroid drugs synthetic key intermediate, be used for steroid drugs production at present, people still expect to have more advanced method to satisfy the development in market.
Order of the present invention provides the method that a kind of degradation of steroid sapogenin becomes NSC 37741.Specifically replace the chromic anhydride false steroid sapogenines of degrading to become the method for corresponding NSC 37741, and obtained satisfied result with hydrogen peroxide.
The inventive method is in organic solvent, in the presence of the metal catalyst or do not have in the presence of the metal catalyst, replace the chromic anhydride false steroid sapogenines of degrading with hydrogen peroxide, add the excessive oxygenant of reductive agent reduction after the reaction, eliminate reaction through parlkaline again and providing NSC 37741.
This method concrete operations step is as follows:
At first become false steroid sapogenines with reference to existing production method high pressure cracking steroid sapogenines.Oxidation, the elimination reaction of carrying out false steroid sapogenines then just can obtain the NSC 37741 product.
Dissolve false steroid sapogenines in polar solvent, add hydrogen peroxide, metal catalyst and acid, the mol ratio of false steroid sapogenines, hydrogen peroxide, metal catalyst and acid is 1: 1.0-4.0: 0.001-1: 0.0005-10 is recommended as 1: 1-2: 0.01-0.1: 0.001-0.01.Be reflected at 0-80 ℃ and carry out, reaction times 0.1-24 hour.It is complete to raw material reaction that chromatogram tracking reacts.Can in potassium acetate/acetate, reflux after the reaction to make in 1 hour and not eliminate completely that 16-ester group-20-ketone all transforms into NSC 37741.Part acetate is removed in decompression, and residue is handled and obtained required NSC 37741 with organic solvent extraction such as hexanaphthene, ether, sherwood oil, extracting solution.Mother liquor is handled and is obtained 3-methyl-δ-butyrolactone.
Described steroid sapogenines comprises: diosgenin, sisalagenin, zhimusaponin unit, sapogenin that luxuriant numb sapogenin etc. are natural and the sapogenin analogue that is formed by natural sapogenin modification;
Described metal catalyst comprises: tungstic anhydride, tungstate, molybdic acid anhydride, molybdate, phosphomolybdate, heteropolyacid, heteropolyacid salt etc.
Described acid comprises: carboxylic acids such as the phenylformic acid of acetate, formic acid, propionic acid, butyric acid, phenylformic acid, replacement, phthalic acid, m-phthalic acid; Phenylsulfonic acid, to sulfonic acid and derivatives thereof such as methylsulphonic acid Phenylsulfonic acid, fluoro sulfonic acid; Mineral acids such as sulfuric acid, phosphoric acid, phosphorous acid.
Described polar solvent comprises: methylene halide, haloform, ethylene dichloride, acetate, tetrahydrofuran (THF), ether, isopropyl ether, the trimethyl carbinol, dioxane, methyl-sulphoxide, N, proton or aprotic polar solvents such as dinethylformamide, acetone, butanone, acetonitrile, ethyl acetate;
Reductive agent comprises: S-WAT, sodium bisulfite, pyrosulphite hydrogen sodium, Sulfothiorine, vat powder etc.;
Help to understand the present invention by following examples, but be not limited to the present invention.
The oxidative degradation of embodiment 1 false luxuriant numb sapogenin acetic ester and chromic anhydride: the false luxuriant numb sapogenin acetic ester of dissolving 250mg (0.5mmol) is in 1ml acetate, drip chromic anhydride acetic acid solution (112.5mg (1.13mmol) chromic anhydride be dissolved in the 0.9ml acetate promptly), stirring at room reaction 2.5 hours, add 0.05ml formaldehyde decomposing excessive oxygenant, add the 125mg potassium acetate, be warming up to 100 ℃, continued stirring reaction 1 hour, termination reaction.Reaction mixture is removed part acetate through underpressure distillation, after the gained residue impouring frozen water, separates out throw out, filtration, washing, the dry reacting coarse product that gets.Reacting coarse product is through silica gel column chromatography (eluent: petrol ether/ethyl acetate=12/1) obtain 118mg degraded product NSC 37741 acetic ester, yield 65.9%.M.p.162-64 ℃, infrared spectra (ν): 2924,2846,1737,1675,1587,1243,1031cm
-1Hydrogen nuclear magnetic resonance spectrum (300NHz, CDCl
3) δ: 6.60 (dd, J=1.3Hz, 1H, 16-H), 4.6 (m, 1H, 3-H), 2.01 (s, 3H, 3-CH
3COO-), 2.26 (s, 3H, CH
3CO-, 21-H), 0.85 (s, 3H, 18-H), 0.88 (s, 3H, 19-H) the ppm. mass spectrum (m/z, %) 417 (M+1), 373 (10.60), 356 (28.36), 281 (15.65), 253 (19.38), 43 (100).
The oxidative degradation of the false luxuriant numb sapogenin acetic ester of embodiment 2 and catalytic amount chromic anhydride and hydrogen peroxide: the luxuriant numb sapogenin acetic ester of dissolving 250mg (0.5mmol) vacation in 1ml acetate, add chromic anhydride (5mg, 0.05mmol), hydrogen peroxide (30%H
2O
2, 204 μ l, 2mmol) acetate (1ml) solution.Reaction mixture after 3 hours, adds the 125mg potassium acetate, 2ml bisulfite saturated aqueous solution of sodium in the stirring at room reaction, continued stirring reaction 1 hour at 100 ℃, acetate is removed in underpressure distillation must react thick 180mg, obtains 103mg NSC 37741 acetic ester, yield 57.5% through silica gel column chromatography again.Spectral data is with embodiment 1.
Embodiment 3 false luxuriant numb sapogenin acetic ester and hydrogen peroxide oxidation DeRs: dissolve the false luxuriant numb sapogenin acetic ester of 250mg (0.5mmol) in 2ml acetate, hydrogen peroxide (30%H
2O
2, 204 μ l, 2mmol).The gained reaction mixture after 2.5 hours, adds the 125mg potassium acetate in the stirring at room reaction, and the saturated aqueous solution of sodium bisulfite of 2ml continued stirring reaction 1 hour at 100 ℃, removed most of solvent under reduced pressure, added frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product 303mg, and (eluent: petrol ether/ethyl acetate=12/1) obtain 80mg degraded product NSC 37741 acetic ester, yield 44.7%. spectral data is with embodiment 1 through silica gel column chromatography.
The oxidative degradation of embodiment 4 false luxuriant numb sapogenin acetic ester and catalytic amount molybdic anhydride and hydrogen peroxide: the false luxuriant numb sapogenin acetic ester of dissolving 125mg (0.25mmol) adds MoO in 2ml acetone
37mg (0.05mmol), 4MH
3PO
41, hydrogen peroxide (30%H
2O
2, 102 μ l, 1mmol).The gained reaction mixture was stirring at room 6 hours, and raw material is complete reaction not, and back flow reaction is 2 hours again, and solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 2.5ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds 0.5mlHOAc and 63mg KOAc after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain 62mg degraded product NSC 37741 acetic ester, yield 68.8%.Spectral data is with embodiment 1.
The oxidative degradation of embodiment 5 false luxuriant numb sapogenin acetic ester and catalytic amount tungstic anhydride and hydrogen peroxide: the false luxuriant numb sapogenin acetic ester of dissolving 500mg (1mmol) adds WO in 8ml acetone
346mg (0.2mmol), 4M H
3PO
44, hydrogen peroxide (30%H
2O
2, 408 μ l, 4mmol), gained reaction mixture refluxed stirring reaction 6 hours.Solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 10ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds HOAc2ml and KOAc250mg after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain 205mg degraded product NSC 37741 acetic ester, yield 58.7%.Spectral data is with embodiment 1.
The oxidative degradation of embodiment 6 false luxuriant numb sapogenin acetic ester and catalytic amount Sodium orthomolybdate and hydrogen peroxide: the false luxuriant numb sapogenin acetic ester of dissolving 500mg (1mmol) adds Na in 8ml acetone
2MoO
42H
2O 48mg (0.2mmol), 4M H
3PO
44, hydrogen peroxide (30%H
2O
2, 408 μ l, 4mmol).Gained reaction mixture refluxed stirring reaction 2.5 hours, solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 10ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds HOAc2ml and KOAc250mg after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain 228mg degraded product NSC 37741 acetic ester, yield 63.4%.Spectral data is with embodiment 1.
The oxidative degradation of embodiment 7 false luxuriant numb sapogenin acetic ester and catalytic amount sodium wolframate and hydrogen peroxide: the false luxuriant numb sapogenin acetic ester of dissolving 500mg (1mmol) adds Na in 8ml acetone
2WO
42H
2O 66mg (0.2mmol), 4M H
3PO
44, hydrogen peroxide (30%H
2O
2, 408 μ l, 4mmol).Gained reaction mixture refluxed stirring reaction 0.5 hour, solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 10ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds 2ml HOAc and 250mg KOAc after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain 180mg degraded product NSC 37741 acetic ester, yield 59.2%.Spectral data is with embodiment 1.
The oxidative degradation of embodiment 8 false luxuriant numb sapogenin acetic ester and catalytic amount sodium wolframate and hydrogen peroxide: the false luxuriant numb sapogenin acetic ester of dissolving 125mg (0.25mmol) adds Na in the 1ml dioxane
2WO
42H
2O 8mg (0.024mmol), 4M H
3PO
41, hydrogen peroxide (30%H
2O
2, 102 μ l, 1mmol).Gained reaction mixture stirring at room reaction 3 days.Solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 2.5ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds 0.5mlHOAc and 63mg KOAc after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain 63mg degraded product NSC 37741 acetic ester, yield 70%.Spectral data is with embodiment 1.
The oxidative degradation of embodiment 9 false luxuriant numb sapogenin acetic ester and catalytic amount sodium wolframate and hydrogen peroxide: with the luxuriant numb sapogenin acetic ester 500mg of vacation (1mmol), trimethyl carbinol 4ml, Na
2WO
42H
2O 33mg (0.1mmol), 4M H
3PO
44, hydrogen peroxide (30%H
2O
2, 408 μ l 4mmol) drop in the reaction flask, gained reaction mixture stirring reaction 5.5 hours in 50 ℃ of oil baths.Solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 10ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds HOAc2ml and KOAc250mg after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain 298mg degraded product NSC 37741 acetic ester, yield 82%.Spectral data is with embodiment 1
The oxidative degradation of embodiment 10 false luxuriant numb sapogenin acetic ester and catalytic amount molybdic anhydride and hydrogen peroxide: with the false luxuriant numb sapogenin acetic ester of 250g (0.5mmol), trimethyl carbinol 2ml, MoO
329mg (0.2mmol), C
6H
5CO
2H 122mg (1mmol), hydrogen peroxide (30%H
2O
2, 204 μ l 2mmol) drop in the reaction flask, gained reaction mixture stirring reaction 4 hours in 50 ℃ of oil baths.Solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 10ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds HOAc1ml and KOAc125mg after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, and (eluent: petrol ether/ethyl acetate=10/1) obtain 156mg degraded product NSC 37741 acetic ester, yield 87.6%. spectral data is with embodiment 1 through silica gel column chromatography
The oxidative degradation of embodiment 11 false luxuriant numb sapogenin acetic ester and catalytic amount molybdic anhydride and hydrogen peroxide: with the false luxuriant numb sapogenin acetic ester of 500mg (1mmol), trimethyl carbinol 4ml, MoO
358mg (0.4mmol), m-phthalic acid 166mg (1mmol), hydrogen peroxide (30%H
2O
2, 408 μ l 4mmol) drop in the reaction flask, gained reaction mixture stirring reaction 3.5 hours in 35 ℃ of oil baths.Add saturated NaHSO
3Solution is removed excessive H
2O
2, to filter, the hexanaphthene extracting of filtrate evaporate to dryness, excess with the extract evaporate to dryness, adds HOAc 4ml, KOAc250mg, back flow reaction 2 hours.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product 506mg, and (eluent: petrol ether/ethyl acetate=10/1) obtain 239mg degraded product NSC 37741 acetic ester, yield 67.1%. spectral data is with embodiment 1. through silica gel column chromatography
The oxidative degradation of embodiment 12 false luxuriant numb sapogenin acetic ester and catalytic amount phospho-molybdic acid and hydrogen peroxide: the false luxuriant numb sapogenin acetic ester of dissolving 500mg (1mmol) adds 186mg H in 2ml acetone
7[(PMo
2O
7)
6] xH
2O (0.1mmol), 4MH
3PO
44, hydrogen peroxide (30%H
2O
2, 408 μ l, 4mmol).Gained reaction mixture stirring at room 4 hours, the raw material unreacted is complete, continues stirring reaction 3 hours in 60 ℃ of oil baths, and solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 10ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds 4ml HOAc and 250mg KOAc after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain 301mg degraded product NSC 37741 acetic ester, yield 84%.Spectral data is with embodiment 1.
The oxidative degradation of embodiment 13 false zhimusaponin unit's acetic ester and catalytic amount molybdic anhydride and hydrogen peroxide: with the false zhimusaponin of 250g (0.5mmol) unit acetic ester, the 2ml trimethyl carbinol, 29mg MoO
3(0.2mmol), 122mg C
6H
5CO
2H (1mmol), hydrogen peroxide (30%H
2O
2, 204 μ l 2mmol) drop in the reaction flask, gained reaction mixture stirring reaction 4 hours in 50 ℃ of oil baths.Solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 10ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds 1ml HOAc and 125mg KOAc after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain 150mg degraded product 5 β-NSC 37741 acetic ester, yield 83.8%.m.p.144-6 ℃, infrared spectra (ν): 2924,2845,1738,1674,1586,1245,1030cm
-1Hydrogen nuclear magnetic resonance spectrum (300MHz, CDCl
3) δ: 6.61 (dd, J=1.3Hz, 1H, 16-H), 4.62 (m, 1H, 3-H), 2.01 (s, 3H, 3-CH
3COO-), 2.26 (s, 3H, CH
3CO-, 21-H), 0.84 (s, 3H, 18-H), 0.88 (s, 3H, 19-H) the ppm. mass spectrum (m/z, %) 417 (M+1), 373 (10.60), 356 (28.36), 281 (15.65), 253 (19.38), 43 (100).
The oxidative degradation of embodiment 14 false diosgenin acetic ester and catalytic amount sodium wolframate and hydrogen peroxide: with false diosgenin acetic ester 500mg (1mmol), trimethyl carbinol 4ml, Na
2WO
42H
2O 33mg (0.1mmol), 4M H
3PO
44, hydrogen peroxide (30%H
2O
2, 408 μ l 4mmol) drop in the reaction flask, gained reaction mixture stirring reaction 5.5 hours in 50 ℃ of oil baths.Solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 10ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds HOAc2ml and KOAc250mg after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain the pregnant diketene alcohol acetic ester of 297mg degraded product, yield 82%.M.p.176 ℃, infrared spectra (ν): 2966,2945,1731,1662,1585,1248,1234,1030cm
-1Hydrogen nuclear magnetic resonance spectrum (300MHz, CDCl
3) δ: 6.61 (dd, J=1.3Hz, 1H, 16-H), 5.04 (d, J=4Hz, 1H, 6-H), 4.62 (m, 1H, 3-H), 2.01 (s, 3H, 3-CH
3COO-), 2.26 (s, 3H, CH
3CO-, 21-H), 0.84 (s, 3H, 18-H), 0.88 (s, 3H, 19-H) the ppm. mass spectrum (m/z, %) 415 (M+1), 371 (10.60), 354 (28.36), 279 (15.65), 251 (19.38), 43 (100).
The oxidative degradation of embodiment 15 false rockogenin acetic ester and catalytic amount molybdic anhydride and hydrogen peroxide: dissolving 129mg (0.25mmol) rockogenin acetic ester adds 7mg MoO in 2ml acetone
3(0.05mmol), 4MH
3PO
41, hydrogen peroxide (30%H
2O
2, 102 μ l, 1mmol).The gained reaction mixture was stirring at room 6 hours, and raw material is complete reaction not, and back flow reaction is 2 hours again, and solids removed by filtration with the filtrate evaporate to dryness of trying one's best, adds the dilution of 2.5ml water, with CH
2Cl
2Extraction, saturated NaCl solution washing, organic phase adds 0.5mlHOAc and 63mg KOAc after steaming and desolventizing, and refluxes 1 hour.Remove most of solvent under reduced pressure, add frozen water, with CH
2Cl
2Extraction, the extraction liquid washing is dry, and evaporate to dryness gets crude product, through silica gel column chromatography (eluent: petrol ether/ethyl acetate=10/1) obtain 62mg degraded product 12 β-prebediolone acetate alcohol acetic ester, yield 68.8%.M.p.214-5 ℃ of infrared spectra (ν): 2925,2847,1737,1675,1587,1363,1243,1031,984,824,635cm
-1Hydrogen nuclear magnetic resonance spectrum (300MHz, CDCl
3) δ: 6.60 (dd, J=1.3Hz, 1H, 16-H), 4.68 (dd, J=11.3,4.6Hz, 1H, 12-H), 4.6 (m, 1H, 3-H), 2.01 (s, 3H, CH
3COO-), 2.04 (s, 3H, CH
3COO-), 2.26 (s, 3H, CH
3CO-, 21-H), 0.85 (s, 3H, 18-H), 0.88 (s, 3H, 19-H) the ppm. mass spectrum (m/z, %) 417 (M+1), 373 (10.60), 356 (28.36), 281 (15.65), 253 (19.38), 43 (100).
Claims (6)
1, the synthetic method of a kind of new NSC 37741 compound, it is characterized in that in polar solvent, the mol ratio of false steroid sapogenines, hydrogen peroxide, metal catalyst and organic or inorganic acid is 1: 1.0-4.0: 0.001-1: during 0.0005-10,0-80 ℃ of reaction 0.1-24 hour; Described steroid sapogenines is a diosgenin, sisalagenin, zhimusaponin unit, the natural sapogenin of luxuriant numb sapogenin or the sapogenin analogue that is formed by natural sapogenin modification; Described metal catalyst is tungstic anhydride, tungstate, molybdic acid anhydride, molybdate, phosphomolybdate, heteropolyacid, heteropolyacid salt.
2, the synthetic method of a kind of new NSC 37741 compound as claimed in claim 1 is characterized in that the mol ratio of described false steroid sapogenines, hydrogen peroxide, metal catalyst and acid is 1: 1-2: 0.01-0.1: 0.001-0.01.
3, the synthetic method of a kind of new NSC 37741 compound as claimed in claim 1, it is characterized in that described organic acid be the carboxylic acid of the phenylformic acid that comprises acetate, formic acid, propionic acid, butyric acid, phenylformic acid, replacement, phthalic acid, m-phthalic acid and comprise Phenylsulfonic acid, to the sulfonic acid and the derivative thereof of methylsulphonic acid Phenylsulfonic acid, fluoro sulfonic acid.
4, the synthetic method of a kind of new NSC 37741 compound as claimed in claim 1 is characterized in that described mineral acid is the mineral acid that comprises sulfuric acid, phosphoric acid, phosphorous acid
5, the synthetic method of a kind of new NSC 37741 compound as claimed in claim 1 is characterized in that after reaction product refluxed 1 hour in potassium acetate/acetate, and part acetate, residue organic solvent extraction are removed in decompression.
6, the synthetic method of a kind of new NSC 37741 compound as claimed in claim 1, it is characterized in that described polar solvent is to comprise methylene halide, haloform, ethylene dichloride, acetate, tetrahydrofuran (THF), ether, isopropyl ether, the trimethyl carbinol, dioxane, methyl-sulphoxide, N, dinethylformamide, acetone, butanone, acetonitrile, ethyl acetate are at interior proton or aprotic polar solvent.
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| WO2005007668A1 (en) * | 2003-07-16 | 2005-01-27 | Shanhghai Institute Of Organic Chemistry, Chinese Academy Of Sciences | A production process for 16-dehydropregnenoneol and its analogs |
| CN101974057A (en) * | 2010-10-13 | 2011-02-16 | 天津大学 | Preparation method of 16-dehydropregnenolone acetate and 16-dehydropregnenolone acetate congeners |
| CN102286052A (en) * | 2011-07-13 | 2011-12-21 | 中国科学院上海有机化学研究所 | Method for synthetising pregnenolol compound |
| CN102329368A (en) * | 2011-07-13 | 2012-01-25 | 中国科学院上海有机化学研究所 | 20 alpha,22 beta,23 alpha-trihydroxy steroidal compound, and synthesis method and application thereof |
| CN102391343A (en) * | 2011-08-31 | 2012-03-28 | 天津大学 | Method for synthetizing dehydropregnenolone acetate and isotype substance thereof |
| CN103864873A (en) * | 2014-04-02 | 2014-06-18 | 中国科学院上海有机化学研究所 | 16-(2'-hydroxyl-4'-methyl-5'-acetoxyl) amyl acyloxy acetic acid progesterone alcohol compound as well as synthetic method and application thereof |
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2001
- 2001-06-29 CN CNB011131969A patent/CN1146574C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005007668A1 (en) * | 2003-07-16 | 2005-01-27 | Shanhghai Institute Of Organic Chemistry, Chinese Academy Of Sciences | A production process for 16-dehydropregnenoneol and its analogs |
| CN101974057A (en) * | 2010-10-13 | 2011-02-16 | 天津大学 | Preparation method of 16-dehydropregnenolone acetate and 16-dehydropregnenolone acetate congeners |
| CN102286052A (en) * | 2011-07-13 | 2011-12-21 | 中国科学院上海有机化学研究所 | Method for synthetising pregnenolol compound |
| CN102329368A (en) * | 2011-07-13 | 2012-01-25 | 中国科学院上海有机化学研究所 | 20 alpha,22 beta,23 alpha-trihydroxy steroidal compound, and synthesis method and application thereof |
| CN102286052B (en) * | 2011-07-13 | 2013-03-06 | 中国科学院上海有机化学研究所 | Method for synthetising pregnenolol compound |
| CN102391343A (en) * | 2011-08-31 | 2012-03-28 | 天津大学 | Method for synthetizing dehydropregnenolone acetate and isotype substance thereof |
| CN103864873A (en) * | 2014-04-02 | 2014-06-18 | 中国科学院上海有机化学研究所 | 16-(2'-hydroxyl-4'-methyl-5'-acetoxyl) amyl acyloxy acetic acid progesterone alcohol compound as well as synthetic method and application thereof |
| CN105111268A (en) * | 2015-09-22 | 2015-12-02 | 武汉工程大学 | Preparation method of dehydropregnenolone acetate |
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