CN103626822B - Synthetic method of 25-hydroxycholesterol - Google Patents
Synthetic method of 25-hydroxycholesterol Download PDFInfo
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- CN103626822B CN103626822B CN201310548969.8A CN201310548969A CN103626822B CN 103626822 B CN103626822 B CN 103626822B CN 201310548969 A CN201310548969 A CN 201310548969A CN 103626822 B CN103626822 B CN 103626822B
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Abstract
The invention discloses a synthetic method of 25-hydroxycholesterol. The synthetic method comprises the following steps: (1) protecting 3-hydroxy of 24-dehydrocholesterol so a to obtain acylated 24-dehydrocholesterol; (2) carrying out hydroxyhalogenation reaction on double bonds on the 24th site of the product obtained in the step (1), namely reacting the acylated 24-dehydrocholesterol with deionized water and a halogenated agent for 2-4 hours in a solvent at the temperature of -20 DEG C to -1 DEG C; and carrying out aftertreatment on reaction liquid so as to obtain a hydroxyhalogenation product; and (3) reacting the hydroxyhalogenation product with an aluminium hydrogenation reagent for 3-8 hours in the solvent at the temperature of 20-70 DEG C, wherein the molar ratio of the aluminium hydrogenation reagent to the hydroxyhalogenation product is (2-6): 1, and carrying out aftertreatment on reaction liquid, thus obtaining the 25-hydroxycholesterol. The synthetic method of the 25-hydroxycholesterol has the characteristics of simple process, environmental protection, few side reactions and high yield.
Description
Technical field
The present invention relates to a kind of method being prepared 25-HYDROXY CHOLESTEROL by desmesterol, belong to a kind of method preparing 25-HYDROXY CHOLESTEROL based on hydroxyl halogenation and reductive dehalogenation.
Background technology
Vitamins D
3belong to steroid derivative, the formation for bone has great significance.It can promote the absorption in enteron aisle of calcium, phosphorus, guarantees the content of these two kinds of elements in body fluid, promotes the normal calcification of bone.Human body is deficient in vitamin D
3, can there is rickets in children's, adult then can occur osteomalacia.Vitamins D
3anti-rachitic effect mainly by 1,25-(OH)
2d
3realize, its biological activity intensity is vitamins D
310000 times.Find through a series of research, the hydroxyl of 25-position is vitamins D
3the feature that meta-bolites has jointly, therefore, as synthesis 1,25-(OH)
2d
3important as precursors, the synthesis of 25-HYDROXY CHOLESTEROL can determine its condition of production to a great extent.
In the synthetic method of current bibliographical information, comprise following 2 classes:
1), hydroxyl mercury method synthesis 25-HYDROXY CHOLESTEROL (C.R.Chimie, 6,79-82,2003.).The method, using desmesterol as raw material, adopts mercuric acetate and water to carry out oxymercuration reaction, and the temperature of reaction of oxymercuration reaction is room temperature, and yield is 85%, and hydroxyl mercury method relates to heavy metal Hg, there is toxicity, pollutes large.
2), the method for epoxidation open loop is again adopted to react.The method using desmesterol as starting raw material, metachloroperbenzoic acid as epoxidation reagent, chloroform as the condition of solvent under carry out epoxidation reaction.Lithium Aluminium Hydride is utilized to carry out open loop (Chem.Pharm.Bull.21 (2), 457-458,1973.) after epoxidation reaction terminates.Epoxidation reaction temperature is about 0 DEG C, and ultimate yield is 50%, and epoxidation step yield is 60%.The major defect of the method is: selectivity is poor, and yield is relatively low.
So, need a rational alternative route at present badly to carry out the production of 25-HYDROXY CHOLESTEROL.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of rational technology, reaction conditions is gentle, and selectivity is high, simple to operate, the preparation method of eco-friendly 25-HYDROXY CHOLESTEROL.
In order to solve the problems of the technologies described above, the invention provides a kind of preparation method of 25-HYDROXY CHOLESTEROL, comprising the following steps:
1), the hydroxyl of compound 3-shown in formula II is protected:
In solvent I, under the katalysis of DMAP (DMAP), under acid binding agent existent condition, desmesterol and carboxylic acid anhydride or acyl chlorides (that is, about 10 ~ 40 DEG C) under 10 DEG C ~ reflux state react 10 ~ 24h; The mol ratio of described desmesterol and carboxylic acid anhydride or acyl chlorides is 1:1.2 ~ 2; DMAP (DMAP) is 0.005 ~ 0.05:1 with the mass ratio of desmesterol consumption; The mol ratio of acid binding agent and desmesterol is 1.8 ~ 10:1;
The reaction solution of gained, through aftertreatment, obtains acidylate desmesterol;
The structural formula of described desmesterol is as shown in following formula II:
2), double bond step 1) obtained on product 24 carries out hydroxyl halogenating reaction:
In solvent II, acidylate desmesterol, deionized water and halide reagent that step 1) is prepared and obtained react 2 ~ 4h at the temperature of-20 ~-1 DEG C; The mol ratio of described acidylate desmesterol and halide reagent is 1:1 ~ 1.5; The acidylate desmesterol adapted 8 ~ 12mL(of described every 1mmol is preferably 10mL) deionized water;
Extraction after the reaction solution dilution of gained, dry after the extraction liquid washing of gained, the dried product exhibited of gained, through pillar layer separation, obtains hydroxyl halogenated products;
3), by step 2) obtained product carries out the dehalogenation reaction, can obtain compound shown in formula I:
In solvent III, step 2) preparation and the hydroxyl halogenated products that obtains and aluminium hydroborating reagent react 3 ~ 8h at the temperature of 20 ~ 70 DEG C; The mol ratio of described aluminium hydroborating reagent and hydroxyl halogenated products is 2 ~ 6:1;
Shrend is utilized to go out aluminium hydroborating reagent excessive in reaction solution after the reaction solution of gained is cooled to room temperature, then successively through pickling and extraction; Dry after the extraction liquid washing of gained, obtain 25-HYDROXY CHOLESTEROL crude product; Described 25-HYDROXY CHOLESTEROL crude product, through recrystallization, obtains 25-HYDROXY CHOLESTEROL;
The structural formula of described 25-HYDROXY CHOLESTEROL is as shown in following formula I:
Improvement as the preparation method of 25-HYDROXY CHOLESTEROL of the present invention: in step 1):
Carboxylic acid anhydride is diacetyl oxide (aceticanhydride), propionic anhydride, butyryl oxide, valeric anhydride, benzoyl oxide, Succinic anhydried or Tetra hydro Phthalic anhydride;
Acyl chlorides is Acetyl Chloride 98Min., propionyl chloride, butyryl chloride or Benzoyl chloride.
Further improvement as the preparation method of 25-HYDROXY CHOLESTEROL of the present invention:
In step 1):
Acid binding agent is triethylamine, diethylamine, quadrol, ammonia, pyridine or piperidines.
Further improvement as the preparation method of 25-HYDROXY CHOLESTEROL of the present invention: step 2) in:
Halide reagent is N-N-halosuccinimides, N, N-dibromo para toluene sulfonamide (TsNBr
2), C5H6Br2N2O2 (DBDMH) or tribromo tricarbimide (TBCA).
Further improvement as the preparation method of 25-HYDROXY CHOLESTEROL of the present invention:
Described N-N-halosuccinimides is N-chlorosuccinimide (NCS) or N-bromo-succinimide (NBS).
Further improvement as the preparation method of 25-HYDROXY CHOLESTEROL of the present invention: described aluminium hydroborating reagent is Lithium Aluminium Hydride, three (tert.-butoxy) lithium aluminum hydride, two (methoxy ethoxy) sodium aluminum hydride (that is, two (methoxy ethoxy) sodium alanate).
In the present invention:
Solvent I used in step 1) is pyridine, methylene dichloride, tetrahydrofuran (THF), toluene etc.; Generally speaking, the solvent I of the desmesterol adapted 100 ~ 200ml of every 0.052mol.
In step 1),
When selecting pyridine, tetrahydrofuran (THF) as solvent I; aftertreatment is: by the reaction solution of gained successively through washing, pickling (dilute hydrochloric acid of 5%) extracts afterwards, and described extraction liquid alkali cleaning (utilizing saturated sodium bicarbonate solution to wash) is to neutral; drying, obtains acidylate desmesterol.
When selecting methylene dichloride, toluene as solvent I; aftertreatment is: by the reaction solution of gained successively after pickling (dilute hydrochloric acid of 5%), alkali cleaning (saturated sodium bicarbonate solution), salt wash (saturated nacl aqueous solution); drying, obtains acetylize desmesterol.
Step 2) in solvent II used be tetrahydrofuran (THF), acetone, butanone, ethyl acetate, methylene dichloride, toluene, the trimethyl carbinol, diglyme; Generally speaking, the solvent II of the acidylate desmesterol adapted 20 ~ 100mL of every 1mmol.
Be tetrahydrofuran (THF) by solvent III used for step 3); Generally speaking, the solvent of the hydroxyl halogenated products adapted 20 ~ 100mL of every 1mmol.
The invention belongs to a kind of method preparing 25-HYDROXY CHOLESTEROL based on hydroxyl halogenation and reductive dehalogenation.
In step 1): utilize carboxylic acid anhydride or acyl chlorides to protect the hydroxyl on desmesterol 3.
In step 2) in: utilize N-N-halosuccinimides, N, N-dibromo para toluene sulfonamide (TsNBr
2), the halide reagent such as C5H6Br2N2O2 (DBDMH), tribromo tricarbimide (TBCA) and deionized water prepared by step 1) and obtains product---the double bond on 24 of acidylate desmesterol carries out hydroxyl halogenating reaction.
In step 3): utilize and go back original reagent----aluminium hydroborating reagent is to step 2) preparation and the product that obtains---hydroxyl halogenated products carries out reduction dehalogenation reaction.
The preparation method of 25-HYDROXY CHOLESTEROL of the present invention has following technical superiority:
The present invention utilizes N-N-halosuccinimides, N, N-dibromo para toluene sulfonamide (TsNBr
2), C5H6Br2N2O2 (DBDMH), tribromo tricarbimide (TBCA) etc. as halide reagent, side reaction is few; Reaction is carried out at low temperatures, and selectivity is high.Adopt the inventive method to prepare 25-HYDROXY CHOLESTEROL, have that technique is simple, environmental friendliness, side reaction is few, yield is high feature.
Embodiment
Room temperature in following examples refers to 10 ~ 25 DEG C.
The preparation method of embodiment 1, a kind of 25-HYDROXY CHOLESTEROL, carries out following steps successively:
1), using 120mL pyridine as solvent, using 30mL pyridine (about 0.372mol) as acid binding agent, add the desmesterol (about 0.052mol) of 20g, 0.2g4-Dimethylamino pyridine (DMAP), drip 10g(under room temperature and be about 0.097mmol) diacetyl oxide (dripping off for about 30 minutes).Reaction process utilizes TLC to monitor, and drip after terminating under room temperature, continue reaction 10h, reaction terminates.
Reaction solution washing (consumption of water is 50ml × 2); pickling (utilize volumetric concentration be 5% dilute hydrochloric acid solution; consumption is 50ml × 2) after utilize methylene dichloride (consumption is 30ml × 3) to extract; extraction liquid utilizes saturated sodium bicarbonate solution to be washed till neutrality; after anhydrous sodium sulphate (about 5g) is dry, de-dry solvent (namely; methylene dichloride), obtain acetylize desmesterol 19.1g, yield is 90.0%.
Yield=actual theoretical amount obtaining quality product/product.
2), with 40mL tetrahydrofuran (THF) for solvent, add 0.4226g(and be about 1mmol) acetylize desmesterol, 10mL deionized water, 0.213g(1.2mmol) N-bromo-succinimide (NBS) slowly adds in (add in four batches, about about 1h adds) reaction flask at-10 DEG C in batches; Reaction process utilizes TLC to monitor, insulation (-10 DEG C) reaction 2h.
Reaction solution use water (30ml × 2) dilution of gained, add methylene dichloride (30ml × 3) extraction, gained extraction liquid uses saturated sodium bisulfite solution (30ml × 2), saturated sodium bicarbonate solution (30ml × 2), saturated nacl aqueous solution (30ml) to wash rear anhydrous sodium sulphate (about 5g) drying successively, (namely decompression (0.1MPa) rotary evaporation removes desolventizing, methylene dichloride), obtain white solid (0.52g), this white solid is carried out pillar layer separation.
The particular content of pillar layer separation is: adopt internal diameter to be the glass column of 2cm, 200-300 object silica gel dress post, dry method loading, adopt n-hexane/ethyl acetate=8:1(volume ratio) eluent carry out wash-out, elutriant adopts TLC to detect, and now collects for during hydroxyl brominated solid sterling in elutriant when detecting, through decompression (0.1MPa) rotary evaporation, desolventizing is removed to the effluent liquid collected, hydroxyl brominated solid (that is, hydroxyl brominated product) can be obtained, yield 85%.
3), with 30mL tetrahydrofuran (THF) for solvent, add 0.52g(and be about 1mmol) hydroxyl brominated product, slowly add 0.15g(4mmol under room temperature) and being warming up to 70 DEG C after Lithium Aluminium Hydride, reaction process utilizes TLC to monitor, stopped reaction after 70 DEG C of reaction 4h.
The Lithium Aluminium Hydride utilizing water (100ml) cancellation excessive after the reaction solution of gained is cooled to room temperature, then directly carry out pickling (utilize volumetric concentration be 5% dilute hydrochloric acid solution, consumption is 50ml × 2), methylene dichloride (30ml × 3) extracts, extraction liquid utilizes saturated sodium bicarbonate solution (30ml × 2) successively, saturated nacl aqueous solution (30ml) the rear anhydrous sodium sulphate of washing (about 5g) is dry, (namely decompression (0.1MPa) rotary evaporation removes desolventizing, methylene dichloride), obtain 25-HYDROXY CHOLESTEROL crude product (0.40g), crude product utilizes toluene (10ml) recrystallization, obtain the finished product 25-HYDROXY CHOLESTEROL 0.33g, yield 88%.
The preparation method of embodiment 2, a kind of 25-HYDROXY CHOLESTEROL,
In this embodiment 2, step 1), 2) different from embodiment 1, difference is:
1), using 100mL methylene dichloride as solvent, the desmesterol (about 0.052mol), 0.2gDMAP, the 10.1g(that add 20g are about 0.1mmol) triethylamine, drip 10g(under room temperature and be about 0.097mmol) aceticanhydride.Reaction process utilizes TLC to monitor, and drip under continuing at room temperature after terminating and react 10h, reaction terminates.
Reaction solution uses dilute hydrochloric acid successively, and (volumetric concentration is 5%; consumption 50ml × 2), saturated sodium bicarbonate solution (30ml × 2), saturated nacl aqueous solution (30ml) washing rear anhydrous sodium sulphate (about 5g) drying; decompression (0.1MPa) rotary evaporation is except desolventizing (i.e. methylene dichloride); obtain acetylize desmesterol 19.0g, yield is 90.0%.
2), by 0.213g(1.2mmol) N-bromo-succinimide (NBS) makes 0.2g(into and is about 1.5mmol) N-chlorosuccinimide (NCS), make temperature of reaction into-1 DEG C by-10 DEG C; All the other are equal to the step 2 of embodiment 1); Yield is 60%.
The preparation method of embodiment 3, a kind of 25-HYDROXY CHOLESTEROL,
In this embodiment 3, step 1), 2) different from embodiment 1, difference is:
1), using 100mL methylene dichloride as solvent, add desmesterol (about 0.052mol), the 0.2gDMAP of 20g, 10.1g(is about 0.1mmol) triethylamine, drip 14.1g(under room temperature and be about 0.1mol) Benzoyl chloride, backflow (about 40 DEG C) is warming up to after dropping terminates, reaction process utilizes TLC to monitor, and terminates reaction after back flow reaction 24h.
Reaction solution is successively with dilute hydrochloric acid, saturated sodium bicarbonate solution, the rear anhydrous sodium sulfate drying of saturated nacl aqueous solution washing, and decompression rotary evaporation is except desolventizing, and obtain benzoylation desmesterol 23.2g, yield is 95.0%.
2), by 0.213g(1.2mmol) N-bromo-succinimide (NBS) makes 0.29g(into and is about 1.0mmol) C5H6Br2N2O2, make temperature of reaction into-20 DEG C by-10 DEG C; All the other are equal to the step 2 of embodiment 1); Yield is 58%.
The preparation method of embodiment 4, a kind of 25-HYDROXY CHOLESTEROL,
In this embodiment 4, step 2) different from embodiment 1, difference is:
By 0.213g(1.2mmol) N-bromo-succinimide (NBS) makes 0.40g(into and is about 1.1mmol) N, N-dibromo para toluene sulfonamide, make solvent into methylene dichloride by tetrahydrofuran (THF); All the other are equal to the step 2 of embodiment 1); Yield is 80%.
The preparation method of embodiment 5, a kind of 25-HYDROXY CHOLESTEROL,
In this embodiment 5, step 2) different from embodiment 1, difference is:
By 0.213g(1.2mmol) N-bromo-succinimide (NBS) makes 0.365g(into and is about 1.0mmol) tribromo tricarbimide, make solvent into acetone by tetrahydrofuran (THF); All the other are equal to the step 2 of embodiment 1); Yield is 52%.
The preparation method of embodiment 6, a kind of 25-HYDROXY CHOLESTEROL,
In this embodiment 6, step 3) is different from embodiment 1, and difference is:
By 0.15g(4mmol) Lithium Aluminium Hydride makes three (tert.-butoxy) lithium aluminum hydride (1.5g, 6mmol) into; Make temperature of reaction into 40 DEG C by 70 DEG C, the reaction times makes 6h into by 4h; All the other are equal to the step 3) of embodiment 1; Yield is 85%.
The preparation method of embodiment 7, a kind of 25-HYDROXY CHOLESTEROL,
In this embodiment 7, step 3) is different from embodiment 1, and difference is:
By 0.15g(4mmol) Lithium Aluminium Hydride makes two (methoxy ethoxy) sodium aluminum hydride (0.61g, 3mmol) into; Make temperature of reaction into 30 DEG C by 70 DEG C, the reaction times makes 8h into by 4h; All the other are equal to the step 3) of embodiment 1; Yield is 87%.
Comparative example 1, step 2 relative to embodiment 1) do to change as follows:
Temperature of reaction is risen to 20 DEG C by-10 DEG C, and all the other are equal to the step 2 of embodiment 1); The yield of this step is only 40%.
Comparative example 2, step 2 relative to embodiment 1) do to change as follows:
In step 2) in, the consumption of deionized water is reduced to 1mL by 10mL, and all the other are equal to the step 2 of embodiment 1); It is 49% that the yield of this step is only yield.
Comparative example 3, do following change relative to the step 3) of embodiment 1:
In step 3), Lithium Aluminium Hydride is changed into sodium borohydride (molar weight is constant), all the other are all same as the step 3) of embodiment 1; Finally product cannot be obtained.
Comparative example 4, step 2 relative to embodiment 1) do to change as follows:
In step 2) in, NBS is replaced by bromine water (molar weight is constant), all the other are equal to the step 2 of embodiment 1); The yield of this step is only 23%.
Finally, it is also to be noted that what enumerate above is only some specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be had.All distortion that those of ordinary skill in the art can directly derive from content disclosed by the invention or associate, all should think protection scope of the present invention.
Claims (6)
- The preparation method of 1.25-hydroxycholesterol, is characterized in that comprising the following steps:1), the hydroxyl of compound 3-shown in formula II is protected:In solvent I, under the katalysis of DMAP, under acid binding agent existent condition, desmesterol and carboxylic acid anhydride or acyl chlorides react 10 ~ 24h under 10 DEG C ~ reflux state; The mol ratio of described desmesterol and carboxylic acid anhydride or acyl chlorides is 1:1.2 ~ 2; The mass ratio of DMAP and desmesterol consumption is 0.005 ~ 0.05:1; The mol ratio of acid binding agent and desmesterol is 1.8 ~ 10:1;The reaction solution of gained, through aftertreatment, obtains acidylate desmesterol;The structural formula of described desmesterol is as shown in following formula II:2), by step 1) double bond on obtained product 24 carries out hydroxyl halogenating reaction:In solvent II, step 1) preparation and the acidylate desmesterol, deionized water and the halide reagent that obtain react 2 ~ 4h at the temperature of-20 ~-1 DEG C; The mol ratio of described acidylate desmesterol and halide reagent is 1:1 ~ 1.5; Acidylate desmesterol adapted 8 ~ 12mL deionized water of described every 1mmol; Described halide reagent is N-N-halosuccinimides, N, N-dibromo para toluene sulfonamide, C5H6Br2N2O2 or tribromo tricarbimide;Extraction after the reaction solution dilution of gained, dry after the extraction liquid washing of gained, the dried product exhibited of gained, through pillar layer separation, obtains hydroxyl halogenated products;3), by step 2) obtained product carries out the dehalogenation reaction, can obtain compound shown in formula I:In solvent III, step 2) preparation and the hydroxyl halogenated products that obtains and aluminium hydroborating reagent react 3 ~ 8h at the temperature of 20 ~ 70 DEG C; The mol ratio of described aluminium hydroborating reagent and hydroxyl halogenated products is 2 ~ 6:1;Shrend is utilized to go out aluminium hydroborating reagent excessive in reaction solution after the reaction solution of gained is cooled to room temperature, then successively through pickling and extraction; Dry after the extraction liquid washing of gained, obtain 25-HYDROXY CHOLESTEROL crude product; Described 25-HYDROXY CHOLESTEROL crude product, through recrystallization, obtains 25-HYDROXY CHOLESTEROL;The structural formula of described 25-HYDROXY CHOLESTEROL is as shown in following formula I:
- 2. the preparation method of 25-HYDROXY CHOLESTEROL according to claim 1, is characterized in that described step 1) in:Carboxylic acid anhydride is diacetyl oxide, propionic anhydride, butyryl oxide, valeric anhydride, benzoyl oxide, Succinic anhydried or Tetra hydro Phthalic anhydride;Acyl chlorides is Acetyl Chloride 98Min., propionyl chloride, butyryl chloride or Benzoyl chloride.
- 3. the preparation method of 25-HYDROXY CHOLESTEROL according to claim 2, is characterized in that described step 1) in:Acid binding agent is triethylamine, diethylamine, quadrol, ammonia, pyridine or piperidines.
- 4. the preparation method of 25-HYDROXY CHOLESTEROL according to claim 3, is characterized in that:Described N-N-halosuccinimides is N-chlorosuccinimide or N-bromo-succinimide.
- 5. the preparation method of 25-HYDROXY CHOLESTEROL according to claim 4, is characterized in that described step 3) in:Described aluminium hydroborating reagent is Lithium Aluminium Hydride, three (tert.-butoxy) lithium aluminum hydride, two (methoxy ethoxy) sodium aluminum hydride.
- 6. the preparation method of 25-HYDROXY CHOLESTEROL according to claim 5, is characterized in that described step 2) in:The acidylate desmesterol adapted 10mL deionized water of every 1mmol, the N-bromo-succinimide of 1.2mmol; Temperature of reaction is-10 DEG C, and the reaction times is 2 ~ 3 hours.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3868396A (en) * | 1973-02-16 | 1975-02-25 | Eisai Co Ltd | Preparation of 25-hydroxycholesterol and esters thereof |
| CN102060902A (en) * | 2011-01-21 | 2011-05-18 | 郑州大学 | Chenodeoxycholic acid synthesis method |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3868396A (en) * | 1973-02-16 | 1975-02-25 | Eisai Co Ltd | Preparation of 25-hydroxycholesterol and esters thereof |
| CN102060902A (en) * | 2011-01-21 | 2011-05-18 | 郑州大学 | Chenodeoxycholic acid synthesis method |
Non-Patent Citations (2)
| Title |
|---|
| 巨勇等.有机合成化学与路线设计(第2版).《有机合成化学与路线设计(第2版)》.清华大学出版社,2007,129-130. * |
| 王兴明等.基础有机化学.《基础有机化学》.科学出版社,2012,168-169. * |
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