Method of producing psoralene derivatives

专利摘要:
An improved process for obtaining 5-methoxy-psoralene from bergamot oil, a method for preparing the compound 5-hydroxy-psoralene from 5-methoxy-psoralene and a method of making novel psoralene derivatives by replacing the hydrogen atom of the 5-hydroxy group with an R group are disclosed. These compounds are prepared by reacting the 5-hydroxy-psoralene with a halide RX in the presence of sodium hydride. Compounds of particular interest are those of which the radical R is: alkanoyl of not more than 10 carbon atoms; orthoacetoxy-benzoyl; alpha thenoyl; O,O diethyl-phosphono; diethylaminoethyl, and 2'3'4'6' tetra alpha acetyl D-gluco pyranosyl.
公开号:SU747428A3
申请号:SU772484403
申请日:1977-05-27
公开日:1980-07-23
发明作者:Николайски Эккхард
申请人:Фотобио Холдинг Аг (Фирма)；
IPC主号:

专利说明:

gas soot). The average yield (10 experiments) 72-85%.
The resulting 5-hydroxyporalen presents small yellow crystals, m.p. 275 ° C. Molecular Weight 202.17.
Found,%: C 65,32; H 3.24; About 31.60.
C 65.36; H 2.99;
Calculated%
031.65.
Example 2. 5-n-Decanoylphenyl.
In an Erlenmeyer flask or a flat-bottomed flask equipped with an air cooler ending in a calcium chloride tube, a mixture of 30 ml of dimethylformamide (DMF) pure and anhydrous, 1.01 g (5 mmol bergaptol molecular weight 202), is kept under intensive stirring at room temperature for 48 hours ,
1 g (5 mmol, with a slight excess of 6%) of n-decanoyl chloride (freshly distilled) molecular weight of 190.5 and 0.15 g (5 mmol, with an excess of 25%) of sodium hydride of molecular weight 24 The mixture is poured onto ice. The precipitate formed is filtered off with suction or filtered. Then it is dried and recrystallized from ethanol-water (1: 1). The yield of 1.26 g (70%).
The resulting 5-n-decanoyl-oxypsoralen is colorless cipher crystals or very thin colorless needles, m.p. , HepcicTBOrim in water, soluble in alcohols, glycols, and vegetable oils.
Found,%: C 70.67, 70.32; And 7.03 7.16.
 Mol. 356.41.
Calculated,%: C, 70.85; H, 6.80.
Thin layer chromatography (Merck 1500 LS-254 silica gel, solvents - cyclohexane: absolute ethanol, 30: 5): Rf 0.80.
Example 3. 5- (o-Acetoxy) -benzoyloxyprene.
In a flask of Example 2, 300 mg (1.4 mmol, with a very small excess) of bergaptol molecular weight 202 are dissolved in 10 ml of chischaego and anhydrous DMF. Then, 42 mg (1.4 mmop, with an excess of 25 %) sodium hydride molecular weight of 24. When the solution becomes homogeneous, a solution of 260 mg (1.4 mmol, with a slight excess) of distilled o-acetoxybenzoyl chloride in 5 ml of pure and anhydrous DMF is added in small portions 5 times. With each addition, a vigorous reaction is observed: the color changes from orange yellow to light yellow.
After that, stirring is continued for another 40 hours. Then the mixture is poured onto broken ice, the precipitate is filtered off with suction, washed several times with cold water, dried and recrystallized from ethanol-water (1: 1). Exit 330 mg (65%). The resulting 5- (o-acetoxy) -benzoyloxypsoralen or psoralen aspirinate is a small, colorless crystals, m.p. 149-151 s, soluble (when heated) in ethanol.
Found,%: C 66.09; H 3.43; 30.63.
ABOUT
Cjo H,., O.,. Mol weight 364,
Calculated,%: C, 66.00; H 3.32;
30.77.
about
Thin layer chromatography (silica gel F-1500 LS-254, solvent; ethyl acetate: ethyl acetate, 80:20): Rf 0.64.
Test for Fe CE ;, negative.
Example 4. 5 - ((L-Tenoyloxy) psoralen.
In the flask of example 2, under vigorous stirring at room temperature for 48 hours, a mixture of 30 ml of pure and anhydrous DMF, 1.01 g (5 mmol) of Bergaptol, molecular weight 202; O, 80 g (5 mmol, with a slight excess) cX -tenoyl chloride with a molecular weight of 146.5 and 0.15 g (6 mmol, with a slight excess) of sodium hydride with a molecular weight of 24. The mixture is poured onto ice, the precipitate is sucked off, dried and crystallized from hot methanol. Yield 1.05 g ().
5- (cX-Tenoyloxy) -psoralen or sulphonated psoralen are small yellow crystals, m.p. 19B-C, insoluble in water, soluble in hot ethanol.
Found,%: C 61.55, 61.55; H 2.60, 2.63; O 25.70, 25.65; S 10.21, 10.09.
S., nd K7 Mol. weight 311.30.
Calculated,%: C, 61.79; H 2.26, O 25.72; S 10.31.
Example 5. The hydrochloride 5- (p-diethylaminoethoxy) - psoralen.
An Erlenmeyer flask or a flat-bottomed flask equipped with an air reflux condenser, ending with a calcium chloride tube, is successively introduced, with vigorous stirring using a magnetic stirrer, 50 ml of pure and anhydrous DMF, 2.02 g (10 im) of bergaptol with a molecular weight of 202, 0, 30 g
0 (12.5 mmol, with an excess, 25%) of sodium hydride of molecular weight 24, and then a solution of 2 g (15 mmol, with an excess of 50%) of diethylaminoethyl chloride (as a base, fresh5 isolated from the corresponding hydrochloride and distilled) molecular weight of 131.5 in 10 ml of anhydrous DMF.
After stirring for 50 hours at room temperature, the reaction mass is poured into 10 ml of cold water, acidified with concentrated hydrochloric acid to pH 3 to completely dissolve the hydrochloride of the product. It is then extracted 3 times, each time using 30 ml of benzene, to remove organic impurities. The base is then made alkaline with concentrated ammonia to pH 10 to isolate the target base (which is extracted 4 times with 50 ml of benzene). The benzene solutions are combined, washed with 30 ml of cold water. Dried over anhydrous sodium sulfate, filtered, the solvent is distilled off (evaporated) and a light yellow color crystals are obtained. They are recrystallized from absolute ethanol and discolored with soot. The resulting 5- (p-diethylaminoethoxy psoralen is a small colorless crystals, m.p. 7611 ° C. Yield 2.40 g (80%). 5-hydrochloride - (- diethylaminoethoxy) -soralen. 1 g of small colorless the crystals are dissolved in anhydrous diethyl ether in 50l.The anhydrous diethyl ether saturated with gaseous hydrogen chloride is then added in small portions up to the maximum precipitation of the desired hydrochloride. Then it is quickly sucked off and washed with anhydrous ether.The yield is quantitative (relative to the base). 5 - (- diethylaminoethoxy) -psoralen hydrochloride is a small, colorless crystals, so that it is soluble in water, hotter than ethanol. Found% g C 59.71, H 6.11 / N 3.88; O 19, 30; CE 10.87. N, d N04-it. Mol. Weight 337.5. Calculated,%: C 60.59; H 5.68; N 4.16; 18.99; se 10.52. Thin-layer chromatography (Merck fl500 LS 254 silica gel, benzene: ethyl acetate: eta. NOL: ammonia, 21: 6: 4: 0.5): Rf 0.31. Test for FeCEj negative. Example 6. 5 - (( , 0-Diethylphosphono) -oxy} - psoralen. In the flask of Example 5, I stirred vigorously for 8 hours at a room temperature of 500 mg (2.5 mmol) of bergaptol, molecular weight 202, 20 mg (5 mmol) of pure and anhydrous triethylamine molecular weight 101 used to absorb hydrogen chloride, which is released during the reaction, and 483 mg (2.8% of freshly distilled diethylchlorophosphate, molecular weight 172.5, dissolved in 10 ml of pure and freshly distilled DMF. Excess DMF and triethylamine are then removed under high vacuum and preferably at room temperature, residue after evaporation The chloroform solution is washed with ice-cold 230 water, then several times with 5% -HhiiM sodium bicarbonate solution until neutral with industrial water. The last time is washed with anhydrous ether. Small crystals of a pink-cream color are obtained, Recrystallized from absolute ethanol and colorless small crystals are obtained. The yield is 465 mg (55%). 5- ((0,0-Diethylphosphono) -oxy)) -soralen or phosphate diethylfurocoumarn or phosphorylated psoralen has the following physicochemical characteristics: fine b colorless crystals, so pl. 99-100 ° C, soluble in hot alcohols. The gross formula is CjgBq O P. Mol. Weight 337.25. Elementar - Calculated Total Analysis,%: 53.46 53.38-53.30 4.52 9.28-9.52 O33.23 Thin layer chromatography (Merck F1500 LS254 silica gel, solvent - benzene: etchschette: ethanol, 21 : 6: 4): Rf 0.67. FeCj test is negative. Example 7, 3, 4, 6-tetraschetis-l-0-gl1ocopyranosyloxy-psoralen. Under vigorous stirring with a magnetic stirrer, 606 mg (3 gFul) of bergaptol with a molecular weight of 202 in 20 ml of pure and anhydrous daph are dissolved with vigorous stirring, then 85 mg of sodium hydride (3.2 mmol) is added, continuing the stirring until clear solution. Further, 1.32 g (3.2 mmol) of acetobromglucose of molecular weight 411, dissolved in 10 ml of anhydrous DMF, are added to the solution and the mixture is further stirred for 2 hours. The reaction mass is poured into 150 ml of cold water. After a few hours, the formation of a light yellow precipitate is observed. It is sucked off and recrystallized from absolute ethanol. The product yield in the form of small yellow crystals 720 mg (45%). Gross formula CjcHp.Oij. Mol. weight 532.38, Found Calculated Elementary analysis, but 55, 98-55.96 4.85-4.80 39.28-39.32. Characteristic: small yellow crystals, so pl. 126-128 ° C, moderately soluble in water, soluble in ethanol (when heated).
Thin layer chromatography: silica gel F-1500 LS-254; solvents benzene: ethanol 30:10 Rf 0.73.
FeCB test, negative.

权利要求:
Claims (1)
[1]
1. Carrer P. The Course of Organic Chemistry. L, 1960, p. 540.

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引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

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US3244729A|1966-04-05|Dimethoxy-x-methyl-g,y-furanocou-marin compounds |

---

US2345635A|1942-04-11|1944-04-04|Wisconsin Alumni Res Found|Di-esters of 3,3'-methylenebis and process of making them|

---

US2889337A|1956-07-19|1959-06-02|William L Stanley|Isolation of furocoumarins|

---

US3201421A|1962-05-09|1965-08-17|Dept Of Chemistry|Preparation of alkyl psoralens|

---

US3553236A|1968-12-06|1971-01-05|Franco Indian Pharmaceuticals|Psoralene and isopsoralene, process for their isolation and separation|

---

US3985896A|1975-07-15|1976-10-12|Smithkline Corporation|Benzophenalenofurans|US5200425A|1976-08-04|1993-04-06|Goupil Jean Jacques|Drugs containing a psoralene derivative|

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US5360816A|1977-05-05|1994-11-01|Goupil Jean Jacques|5-methoxy psoralen used to treat psoriasis|

---

US4324703A|1979-12-26|1982-04-13|Amerchol Corporation|Polyol fragrance fixatives|

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US4264478A|1978-10-30|1981-04-28|Amerchol Corporation|Polyol fragrance fixatives|

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US4269851A|1979-09-10|1981-05-26|Thomas C. Elder, Inc.|8-Aminoalkyl-4-alkylpsoralens|

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FR2695036B1|1992-09-03|1994-10-28|Goupil Jean Jacques|Oil containing 5-methoxypsoralen at a concentration of 60 to 100 PPM and its use for the treatment of psoriasis.|

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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CH668876A|CH614957A5|1976-05-28|1976-05-28|

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