CN108276464A - A kind of preparation method of 3 Alpha-hydroxy -5 α, 14 β-androstane -15- alkene -17- ketone - Google Patents
A kind of preparation method of 3 Alpha-hydroxy -5 α, 14 β-androstane -15- alkene -17- ketone Download PDFInfo
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- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
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Abstract
The invention belongs to the field of chemical synthesis, it is related to a kind of 3 α hydroxyls of compound, 5 α, the preparation method of 14 β androstanes, 15 alkene, 17 ketone, this method is to utilize 3 α hydroxyls of natural steroid, 5 α, 14 α androstanes, 17 ketone is raw material and bromination reactive ketone, then the obtained target product of the step of acting on lower isomerization at alkene, acid base catalysator through dehydrobromination.The present invention provides a kind of 3 α hydroxyls of noval chemical compound, 5 α containing 14 β H, the synthetic method of 14 β androstanes, 15 alkene, 17 ketone, product obtained configuration and α with 14 β H, β unsaturated carbonyl structural units in steroidal rigid backbone have important role to bioactivity.
Description
Technical field
The invention belongs to the field of chemical synthesis, are related to a kind of preparation method of compound, specifically utilize natural steroid 3
- 5 α of Alpha-hydroxy, 14 5 alpha-androsterone-17-ones are raw material, provide a kind of 3 Alpha-hydroxy of noval chemical compound -5 α, 14 β-hero containing 14 β H
The synthetic method of steroid -15- alkene -17- ketone.
Background technology
The chemical modification of natural steroid compound has become the key areas of new drug research, by steroidal female ring structure
Chiral overturning or the modification of function dough, some important steroidal compounds better than parent bioactive can be obtained
[Levina,I.S.；Pokrovskaya,E.V.；Kulikova,L.E.；Kamernitzky,A.V.；Kachala,V.V.；
Smirnov,A.N.Steroids.2008,73,815].Wherein, the chemical modification of more important natural steroid compound be by
14 α H are turned into 14 β H configurations.By configuration reversal, many 14 β H steroidal compounds are provided with special physiological activity, are such as used for
Contraceptive [A.Cleve, G.Neef, E.Ottow, S.Scholz, and W.Schwede, Tetrahedron, 1995,51,
5563-72.], as the inhibitor of sodium pump, for treating heart disease, hypertension, kidney trouble, diabetes, metabolic disorder,
[P.Hilton, J.Hilton, the PCT Int.Appl., 2006120472,16Nov such as tuberculosis, chronic obstructive pulmonary disease and cancer
2006；P.J.Hilton,W.McKinnon,E.C.Gravett,J.-M.R.Peron,C.M.Framptonc,
M.G.Nicholls,G.Lord,Steroids,2010,75,1137–1145.].It can be used as new type nerve steroidal compounds
For GABAAReceptor modulators research [C.Wang, N.P.Rath, D.F.Covey, Tetrahedron, 2007,63 (33),
7977-7984.]。
14 α H of natural steroid be turned into 14 β H can use hydrofluoric acid and antimony pentafluoride system [G.A.Olah,
G.K.S.Prakash,Q.Wang,X.Li,e-EROS Encyclopedia of Reagents for Organic
Synthesis,2001,1-7.].14 α H directly can be turned into 14 β H by the reaction system, but often generate a large amount of by-products,
The configuration efficiency that 14 α H are turned into 14 β H is relatively low, and therefore, this method is difficult to be suitable for produce reality.Research is found by natural
It is halogenated on the positions the α carbon of steroidal D ring 17- carbonyls, hydrogen halides is then eliminated into steroidal D ring 15- alkene -17- ketone, is further tried in alkalinity
The lower isomery of agent effect is at steroidal D ring 14- alkene -17- ketone, then by the tautomerism of D ring 17- carbonyls at D rings 14,16- diene
Alcohol, finally in acid condition at the configuration of 14 β H steroidal D ring 17- carbonyls [A.Cleve, G.Neef, E.Ottow,
S.Scholz, and W.Schwede, Tetrahedron, 1995,51,5563-72.], this method route is long, and conversion ratio is not high.
Halogen can be hydrolyzed into D ring 16- hydroxyl -17- carbonyls under alkaline condition on the positions the α carbon of D ring 17- carbonyls, then exist
Dehydration can obtain the mixture of the steroidal D ring 15- alkene -17- ketone containing 14 α H and 14 β H under acid condition, but detach relatively more tired
Difficult [A.Abad, C.Agullo, M.Arno, L.R.Domingo, and R.J.Zaragoza J.Org.Chem., 1990,55
(8),2369-73.].The mixed system of lithium carbonate and lithium bromide is used from the compound of natural steroid alpha-halogenate D ring 17- carbonyls
Promote to eliminate hydrogen halides, the steroidal D ring 15- alkene -17- ketone of 14 β H of part can be directly obtained, but yield is relatively low, raw material is not
It can make full use of [C.Wang, N.P.Rath, D.F.Covey, Tetrahedron, 2007,63 (33), 7977-7984.].
Invention content
It is raw material that the present invention, which utilizes -5 α of 3 Alpha-hydroxy of natural steroid, 14 5 alpha-androsterone-17-ones (1 in following formula), provides one kind
The preparation method (3b in following formula) of 3 Alpha-hydroxy of noval chemical compound -5 α, 14 β-androstane -15- alkene -17- ketone containing 14 β H, structural formula
It is as follows：
In addition to remaining the due active structure of steroidal in this compound, while retaining 17- carbonyls on steroidal D rings
, α is built in steroidal rigid backbone, beta-unsaturated carbonyl structural unit can be combined with a variety of receptors, show extensive life
Object activity.
To achieve the above objectives, present invention employs following technical scheme, a kind of -5 α of 3 Alpha-hydroxy of compound, 14 β-hero
The preparation method of steroid -15- alkene -17- ketone, includes the following steps：
(a), the synthesis of 3-16 α of Alpha-hydroxy-bromine androstane-17- ketone (2)：
By -5 α of 3 Alpha-hydroxy, 14 5 alpha-androsterone-17-ones (1) generate 3 Alpha-hydroxies -16 with bromination reactive ketone in organic solvent
α-bromine androstane -17- ketone (2)；
(b), the conjunction of 3 Alpha-hydroxy androstane-14- alkene-17- ketone (3a) and 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone (3b)
At：
By 3-16 α of Alpha-hydroxy of step a products therefroms-bromine androstane-17- ketone (2) lithium phosphate effect under dehydrobromination at alkene
3 Alpha-hydroxy androstane-14- alkene-17- ketone (3a) of mixture and 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone (3b) are obtained, is passed through
Chromatography post separation.
(c), finally by the separating obtained 3 Alpha-hydroxy androstane -14- alkene -17- ketone (3a) of compound of step b, in acid base catalysator
Under effect, it is isomerizated into -5 α of 3 Alpha-hydroxy of target product, 14 β-androstane -15- alkene -17- ketone (3b).
Organic solvent in step (a) of the present invention is selected from methanol, ethyl alcohol；The step (b) be by lithium phosphate into
Row debromination；Dicyandiamide solution is Acid-Base System in the step (c)；Used catalyst is optional carbonic acid in the step (c)
Lithium, saleratus, potassium hydroxide, sulfuric acid, p-methyl benzenesulfonic acid or silica gel load sulfuric acid are solid acid catalyst (SSA).The present invention
The step (a) arrives step (c), and reaction conversion ratio is relatively high, and the utilization rate of 3 Alpha-hydroxy androstane -14- alkene -17- ketone of raw material
Height is suitble to mass production.
After the above technical solution is adopted, present invention configuration and α with 14 β H, β-unsaturation carbonyl in steroidal rigid backbone
Based structures unit has important role to bioactivity, from steroidal synthetic degree of angle, because 14 α H of steroidal are turned into 14 β H
Configuration, C (15)=influence of C (16) alkenyls to steroidal female ring, steroidal C (15)-C (16) carry out structural modification can provide spy
Different physiological activity.
Description of the drawings
Fig. 1 is the molecular structure of 3-16 α of Alpha-hydroxy-bromine androstane-17- ketone.
Fig. 2 is the molecular structure of 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone.
Specific implementation mode
With reference to embodiment, the invention will be further described.The raw material used in the present invention is commercialized raw materials,
It can be bought from market.
Scheme 1 synthesizes 3 Alpha-hydroxy androstane-14- alkene-17- ketone (3a) and 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone
The reaction equation of (3b)
The synthesis of 3-16 α of Alpha-hydroxy-bromine androstane-17- ketone (2)
Take -5 5 alpha-androsterone-17-one androsterone of 5.80g (20mmol) 3 Alpha-hydroxy, 11.20g (50mmol) copper bromide, 100mL first
Alcohol is warming up to reflux, TLC tracking reactions in 250ml round-bottomed flasks.8h raw materials react completely.Stop reaction, decompression boils off
Reaction dissolvent methanol in subsequent residue plus 50mL water, extracts liquid separation, organic phase is used successively with dichloromethane (2X 50mL)
50mL is washed 2-3 times, and 25mL saturated nacl aqueous solutions are washed 1-2 times, and organic phase is then collected, and are dried over anhydrous sodium sulfate.Decompression
It boils off methylene chloride and obtains Off-white solid, with recrystallizing methanol, obtain 3-16 α of Alpha-hydroxy of white needles-bromine androstane-
(structural formula such as Fig. 1, crystal parameter are shown in Table 2) 6.5g, yield 88% to 17- ketone (2).
White solid,yield:88%, Mp:154-155oC(PE/AcOEt)；1H-NMR(400MHz,CDCl3)δ
(ppm):4.49 (d, J=6.9Hz, 1H), 4.01 (s, 1H), 2.18 (dd, J=14.4,6.6Hz, 1H), 2.14-2.06 (m,
1H),1.88–1.83(m,1H),0.85(s,3H),0.76(s,3H)13C-NMR(100MHz,DMSO-d6)δ(ppm):213.65,
66.24,54.15,47.94,47.80,46.41,38.96,36.20,35.70,34.25,34.01,32.29,32.00,
30.67,28.90,28.06,19.89,14.19,11.13；IR(KBr,cm-1):3552,2925,2677,1747,1448,
1370,1267,1213,1160,1013,908,835,704,657；HRMS(ESI)calcd for C19H29BrO2Na[M+Na]+
391.1249；Found 391.1243.
The synthesis of 3 Alpha-hydroxy androstane-14- alkene-17- ketone (3a) and 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone (3b)
Take 3-16 α of Alpha-hydroxy of compound-bromine androstane-17- ketone (2) (3.69g, 10mmol), lithium phosphate 1.17g
(10mmol), 60mLDMF are warming up to reflux in round-bottomed flask.TLC tracking reactions, the reaction was complete for 4h raw materials, stops reaction,
It is cooled to room temperature, then system reaction solution is poured into 50mL ice water, it is stirring while adding, there is faint yellow solid precipitation, filters,
Obtain yellow, viscous solid.It after being dissolved with dichloromethane (50mL), is washed 2-3 times with 30mL successively, 15mL saturation foods
Salt is washed 1-2 times, and organic phase, anhydrous sodium sulfate drying are then collected, and decompression boils off methylene chloride and obtains yellow oil,
(petroleum ether is purified through column chromatography:Ethyl acetate=5:1, silica gel), 3 Alpha-hydroxy androstane -14- alkene -17- ketone of white solid is obtained,
1.35g yield：47%；It is continuing with leacheate (petroleum ether:Ethyl acetate=3:1) -14 β of 3 Alpha-hydroxy of faint yellow solid-is obtained
(2) structural formula such as Fig. 2, crystal parameter are shown in Table androstane -15- alkene -17- ketone, 1.33g, yield：46%.
3 Alpha-hydroxy androstane -14- alkene -17- ketone (3a)
White solid,yield:47%, Mp:93-94oC(PE/AcOEt)；1H-NMR(400MHz,CDCl3)δ
(ppm):5.40 (dd, J=4.1,2.0Hz, 1H), 3.97 (dd, J=5.4,2.6Hz, 1H), 2.94-2.87 (m, 1H), 2.74
(m,1H),1.81–1.76(m,1H),1.02(s,3H),0.75(s,3H)；13C-NMR(100MHz,CDCl3)δ(ppm):
223.19,153.60,112.69,66.12,54.68,50.91,41.35,38.65,36.41,35.55,35.39,33.20,
31.92,28.72,28.70,27.88,20.23,19.83,10.95；IR(KBr,cm-1):3416,2929,2863,1717,
1638,1451,1376,1230,1124,1040,904,819,698,612,566；HRMS(ESI)calcd for C19H28O2Na
[M+Na]+311.1987；Found 311.1989.
3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone (3b)
White solid,yield:46%, Mp:172-173oC(PE/AcOEt)；1H-NMR(400MHz,CDCl3)δ
(ppm):7.70 (dd, J=5.9,2.2Hz, 1H), 6.16 (dd, J=5.9,2.3Hz, 1H), 4.02-4.00 (m, 1H), 2.53
(m,1H),1.05(s,3H),0.71(s,3H)；13C-NMR(100MHz,CDCl3)δ(ppm):215.92,164.54,132.97,
66.29,54.84,47.50,45.54,38.95,37.09,35.58,34.04,32.91,31.44,30.79,28.65,
28.48,22.05,19.57,10.11；IR(KBr,cm-1):3504,3048,2928,2861,2648,1691,1577,1448,
1366,1291,1244,1166,1069,1023,973,899,806,705,610,540；HRMS(ESI)calcd for
C19H28O2Na[M+Na]+311.1987；Found311.1988.
3 Alpha-hydroxy androstane-14- alkene-17- ketone (3a) isomerization prepare 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone (3b)
23 Alpha-hydroxy androstane-14- alkene-17- ketone (3a) of Scheme is isomerizated into 3-14 β of Alpha-hydroxy-androstane-15- alkene-
The reaction equation of 17- ketone (3b)
Silica gel load sulfuric acid is the preparation of solid acid catalyst (SSA)：
The method [Zolfigol, M.A.Tetrahedron, 2001,57,9509.] and utilize us that bibliography is reported
The method for the solid acid (SSA) reported prepares [Zhang Yan, Wu's mistake, Chen Tao, Wang Cunde, microwave radiation solid acid catalysis synthesis 4-
Aryl dihydrocoumarin Chemical Industry in Guangzhou, 2010, (12), 94-96.], experimental procedure is as follows：In burnings of the 100ml with absorption plant
Dry silica gel (15g) and anhydrous tetrahydro furan (50ml) are added in bottle, connected on flask equipped with chlorosulfonic acid (5.8g,
Constant pressure funnel 0.05mol).Under stirring, chlorosulfonic acid is added in flask in half an hour, continues to stir half an hour.So
After be evaporated off solvent, dry sealing preserves.Obtained solid acid (SSA) about 2.5mmolg-1。
3 Alpha-hydroxy androstane-14- alkene-17- ketone (3a) are isomerizated into 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone (3b)
Reaction
3 Alpha-hydroxy androstane -14- alkene -17- ketone (3a) (576mg, 2.0mmol) of compound, suitable acid base catalysator
(Table 1) is mixed in 10mL DMF, and reaction system is warming up to reflux.TLC tracking is reacted, and raw material no longer converts after 6h, stops
It only reacts, is cooled to room temperature, filter out solid catalyst, then reaction solution is poured into 20mL ice water, uses dichloromethane
After (2x15mL) extraction, organic phase is washed 2-3 times with 10mL successively, and 10mL saturated common salts are washed 1-2 times, are then collected organic
Phase, anhydrous sodium sulfate drying, the residue that decompression boils off methylene chloride are purified through column chromatography, use leacheate (stone first
Oily ether:Ethyl acetate=5:1, silica gel) 3 Alpha-hydroxy androstane -14- alkene -17- ketone (3a) of recycling, it is continuing with leacheate (oil
Ether:Ethyl acetate=3:1) 3-14 β of Alpha-hydroxy of faint yellow solid-androstane-15- alkene-17- ketone (3b) (Table 1) is obtained.
Table 1.1 3 Alpha-hydroxy androstane -14- alkene -17- ketone (3a) isomerization reaction result
The single crystal analysis of 3-16 α of Alpha-hydroxy-bromine androstane-17- ketone and 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone
Molecular structure such as Fig. 1 of 3-16 α of Alpha-hydroxy-bromine androstane-17- ketone.
Molecular structure such as Fig. 2 of 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone.
The crystal parameter of 2.3-16 α of Alpha-hydroxy of table-bromine androstane-17- ketone and 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone
Claims (3)
1. the preparation method of a kind of -5 α of 3 Alpha-hydroxy of compound, 14 β-androstane -15- alkene -17- ketone, it is characterised in that including as follows
Step：
(a), the synthesis of 3-16 α of Alpha-hydroxy-bromine androstane-17- ketone：
By-5 α of 3 Alpha-hydroxy, it is male that 14 5 alpha-androsterone-17-ones generate 3-16 α of Alpha-hydroxy-bromine with bromination reactive ketone in organic solvent
Steroid -17- ketone；
(b), the synthesis of 3 Alpha-hydroxy androstane-14- alkene-17- ketone and 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone：
By 3-16 α of Alpha-hydroxy of step a products therefroms-bromine androstane-17- ketone, dehydrobromination is mixed at alkene under lithium phosphate effect
3 Alpha-hydroxy androstane-14- alkene-17- ketone of object and 3-14 β of Alpha-hydroxy-androstane-15- alkene-17- ketone, pass through chromatography post separation；
(c), by the separating obtained 3 Alpha-hydroxy androstane -14- alkene -17- ketone of compound of step b, under acid base catalysator effect, isomery
It is melted into -5 α of 3 Alpha-hydroxy of target product, 14 β-androstane -15- alkene -17- ketone.
2. the method as described in claim 1, which is characterized in that the organic solvent in step (a) is methanol or ethyl alcohol.
3. the method as described in claim 1, which is characterized in that dicyandiamide solution is Acid-Base System in step (c)；Used catalyst
For lithium carbonate, saleratus, potassium hydroxide, sulfuric acid, p-methyl benzenesulfonic acid or silica gel load sulfuric acid are solid acid catalyst.
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| CN114933624A (en) * | 2022-05-24 | 2022-08-23 | 大连理工大学 | Method for artificially synthesizing natural product (+) -digitoxin aglycone |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105693801A (en) * | 2016-02-19 | 2016-06-22 | 泰州职业技术学院 | Method for synthesizing 3 beta-hydroxyl-16-aryl androstane-5 (6), 8 (14), 15 (16)-triene-17-ketone |
-
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|---|---|---|---|---|
| CN105693801A (en) * | 2016-02-19 | 2016-06-22 | 泰州职业技术学院 | Method for synthesizing 3 beta-hydroxyl-16-aryl androstane-5 (6), 8 (14), 15 (16)-triene-17-ketone |
Non-Patent Citations (1)
| Title |
|---|
| 粟杨: "具有重要生理活性的甾体D环修饰研究", 《扬州大学硕士学位论文》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114933624A (en) * | 2022-05-24 | 2022-08-23 | 大连理工大学 | Method for artificially synthesizing natural product (+) -digitoxin aglycone |
| CN114933624B (en) * | 2022-05-24 | 2024-02-20 | 大连理工大学 | Artificial synthesis method of natural product (+) -digitonin |
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