• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    An optically active 4-(4-substituted-2,6-dihydroxyphenyl)-6,6-dimethyl-2-norpinanone is reacted with a protonic acid to provide an optical isomer of a cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H- dibenzo[b,d]pyran-9-one. Reaction of said norpinanone with a Lewis acid provides an optical isomer of trans-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9 H-dibenzo[b,d]pyran-9-one. The optically active norpinanones are prepared by reaction of a 5-substituted-resorcinol with an optically active 6,6-dimethyl-2,4-diacetoxy-2-norpinene or an optically active 6,6-dimethyl-2,2-diacetoxy-3-norpinene, which compounds are derived from optically active beta -pinenes.
    公开号:SU786898A3
    申请号:SU772497362
    申请日:1977-07-04
    公开日:1980-12-07
    发明作者:Аллен Арчер Роберт；Аллен Дей Вильям
    申请人:Эли Лилли Энд Компани (Фирма)；
    IPC主号:
    专利说明:

    Preferably, chloroform or benzene is used. The acid used is protonic acid and Lewis acid. If prtonic acid is used, then the product is mainly the optically pure cis form isomer, but if Lewis acid is used, then the product is mainly the trans form. The preferred range for using proton acids are temperatures of 30-80 ° C, and the preferred range for using Lewis acids is temperature up to. The process time is from 8 to 36 hours. The desired products are easily separated by simply washing the reaction of the un.e with Si from the remaining acid with a base, for example, an aqueous solution of sodium bicarbonate, followed by distilling off the solvent. Purification of the product thus obtained can be carried out by standard chromatography, which provides for the separation of 6a, 10a-cishexahydrodibenzopyranone from 6a, 10a trans-derivative. The conversion of the norpinan derivative to the corresponding hexahydrobenzopyranone of formula T is carried out by the reaction of norpinanone with 1-10 molar excess acid, preferably with 1-3 molar excess acid. If necessary, the ba, 10a-cis-hex sagidrodibenzopyranone can be converted to the corresponding 6a, 10a-trans-isomer by reaction with aluminum chloride. Example 1. (-) - 6, b-Dimethyl-2, 4-diacetoxy-2-norpinene. To a solution of 18.0 g of (-) - nopinoneolol acetate in 250 ml of dry benzene stirred under an atmosphere of nitrogen gas, 48.8 g of lead tetraacetate, which was previously dried under vacuum over phosphorus pentoxide and hydroxide, was added at one time. The reaction mixture is heated under reflux and stirred for 18 hours. The reaction mixture is then cooled to room temperature. The mixture is filtered and the filtrate is washed with 10% sodium bicarbonate solution and water, dried, the solvent is distilled off under reduced pressure and 23.5 g of crude product are obtained as a clear liquid. The product thus obtained is distilled and 9.3. G of (-) - b, b-dimethyl-2,4-diacetoxy-2-norepinene is obtained with boiling point 11115 C / W MM.i: o (., 7-89 , (c 1.0, sns.) h Example 2. (, 6-Dimethyl-2, 2-diacetoxy-3-norepinene, To a solution of 18.0 g of (-) - noninonenol acetate in 250% dry dry under stirring in a nitrogen gas atmosphere 48.8 g of lead tetraacetate, which was previously dried under vacuum over phosphorus pentoxide and potassium hydroxide, are added at once to benzene. The reaction mixture is heated under reflux for 2 hours. The mixture is then cooled to room temperature and washed one solution of sodium bicarbonate and water, dried, the solvent is distilled off under reduced pressure and the product is obtained in the form of an oil.The oil is then distilled and 9.8 g of (+) - 6,6-dimethyl-2, 2-diacetoxy-3- are obtained. norpinene with a boiling point of 102-103 ° С / 5 mm.S. + 33.2 ° (с 1.0, СНС1з). С 65.53; Н 7, Calculated,%:, 12. "04Found,%: C 65.77; H 7, COCH3, 36.56. IR: (SCHe): 1750 cm, carbonyl. Example 3. (+) (1,1-Dimethylpentyl) -2,6-dioxyphenyl-6, 6-dimethyl- -2-norpinano. A solution of 1.19 g of (-) -6,6-dimethyl-2, 4-diacetoxy-2-norpine a and 1.18 g of 5- (1,1-dimethylphenyl) -res.; Cin in 50 ml of chloroform containing 0.95 g of p-toluenesulfonic acid monohydrate, kept at 25 ° C for 4 hours. The reaction mixture is then diluted with 100 ml of diethyl alcohol and the resulting solution is washed with 10% aqueous sodium bicarbonate solution, water and dried, the solvent is distilled off under reduced pressure and get the product in the form of a semi-crystalline mass. The product thus formed is triturated with 25 ml of n-hexane and filtered. 1.30 g of ((+) (1,1-dimethylheptyl) -2,6-dioxyphenyl-6, 6-dimethyl-2-norpinanone are obtained. Mp. 171-174 ° C. s (+ 55.8 ( Calculated: С 77.38; Н 9.74Сз НзбОз. Found,%: С 77.59; Н 9.83. IR (KBf) 1668 cm carbonyl. Mass spectrum m / e 372 (M) By the same procedure, 1.18 g of (+) - 6,6-dimethyl-2,2-diacetoxy-3-norepinene was converted into (+) (.1,1-dimethylheptyl) -2, 6- Dioxyphenyl-6,6-dimethyl-2-norpinanone with the same physical properties as the product of Example 3. Example 4. (+) - 4-E4- (1,1-Di. methylheptyl) -2, 6-dioxyphenyl -6,6-dimethyl-2-norpinanone. 238 g of (+) g 6,6-dimethyl-2,2-diacetoxy-3-norepinene and 236 mg of 5- (1,1-dimethylheptyl) - The ezorcine is dissolved in a 12.5 ml dichloromethane flask 8. Equipped with a drying tube. The mixture is cooled to -10 ° C and about 15 mg of boron trifluoride diethylterate is added. The mixture is then stirred for 1.5 hours, then allowed to warm to The solid crystallized out during stirring, the reaction mixture was poured into water, and the organic layer was washed with a 5% aqueous solution of sodium bicarbonate. The organic layer is then dried and evaporated under reduced pressure to a light yellow oil, which is dissolved in hot hexane. After cooling by filtration, {+) - 4- {4-fl, 1-dimethylheptyl) -2,6-di6xyphenyl} -6, b, -dimethyl-2-norpinanone are obtained. The product is identical to the product of example 3.
    PRI, ME 5. (+) - 4-G4- (1,1-Dimethylheptyl) -2,6-dioxyphenyl-6, b-dimethyl-2-norpinanon.
    1 g of (+) - b, b-dimethyl-2,2-diacetoxy-3-norpinene and 1 g of 5- (1,1-dimethylheptyl) -resorcinol are dissolved in 50 ml of a mixture of hexane: diethyl ether (3: 1) and the mixture is cooled to a flask equipped with a drying tube. 0.65 ml of boron trifluoride diethyl etherate is added and the mixture is stirred at -40 ° C for 1 hour. The mixture is then allowed to warm up while stirring for 1 hour. The mixture is then poured onto ice and extracted with diethyl ether. The organic layer is washed twice with a 5% aqueous solution of sodium bicarbonate and dried over sodium sulfate. After evaporation of the dried solvent, a yellow oil is obtained, which is dissolved in a mixture of hexane: cyclohexane, (3: 1) and cooled. In this case, g (+) (1,1-dimethylheptyl) -2, 6-dioxyphenyl-b, b-dimethyl-2-norpinano is obtained, which is identical to the product of example 3.
    Example 6. (+) (1,1-Dimethylheptyl) -2,6-dioxyphenyl-b, b-dimethyl-2-norpinanone.
    9.5 g of (-) - b, 6-dimethyl-2,4-diacetoxy-2-norpinene and 18.9 g of 5- (1,1-dimethylheptyl) -resorcinol are dissolved in 250 ml of chloroform and the solution is cooled to flask equipped with a drying tube. Then 0.5 ml of boron trifluoride diethyl etherate is added and the mixture is stirred at a constant temperature for 2 hours. The mixture is then allowed to warm to 0 ° C and poured into 100 ml of 5% aqueous sodium bicarbonate solution. The aqueous mixture is then extracted with diethylBEJM ether, the organic layer is washed with 5% aqueous sodium bicarbonate solution, dried over sodium sulfate j and evaporated in vacuo to give an oil. This oil is chromatographed on silica gel and eluted with chloroform containing 1-2% methanol and finally diethyl ether. The fractions containing the product are evaporated to dryness and combined. 3.35 g of (+) - 4-y- (1,1-dimethylheptyl) -2,6-dioxyphenyl 6,6-dimethyl-2-nepinanone are obtained after recrystallization from a mixture of cyclohexane / hexane. The product is identical to the product of example 3.
    Example 7. (+) - 4-C4- (1.1-. -Dimethylheptyl) -2, b-dioxyphenyl-6, b-dimethyl-2-nepinanone ..
    238 mg of (-) - 6, b-dimethyl-2,4-diacetoxy-2-norpinene and 236 mg of 5- (1,1-dimethylheptyl) -resorcinol are dissolved in 12.5 MP of benzene and | 198 mg of monohydrate is added para-toluo sulfonic acids. - the mixture is stirred under heating to reflux for 2 hours and diluted after cooling with diethyl ether. The mixture is then washed three times with a 10% aqueous solution of sodium bicarbonate, dried over
    5 sodium sulfate, evaporated in vacuo to obtain 439 mg of a yellow oil. This oil is extracted with hexane, which is distilled off to dryness, and 20 mg of (+) (1,1-dimethylhe1-thyl) -2, 6-dioxyphenyl-6,6-dimethyl-2-nor- is obtained.
    0 penanona, which according to analytical data is identical to the product of example 3.
     Example 8. (+) (G, 1-. -Dimethylheptyl) -2, b-dioxyphenyl-b, b5-dimethyl-2-norpinan.
    340 mg of (, b-dimethyl-2,2-diacetoxy-3-norpinene and 330 mg of 5- (1,1-dimethylheptyl) resorcinol are dissolved in 12.5 ml of dichloromethane at 0 ° C and
    0 is added 50 mg boron trifluoride diethylsferate. The mixture is stirred for 1.5 hours and allowed to warm to room temperature with stirring for another 1 hour. Then
    5 the mixture is poured into water and extracted with diethyl ether. The organic layer is washed with a 5% aqueous solution of sodium bicarbonate, dried and evaporated in vacuo / Me. Get a light yellow oil that is triturated with
    0 15 ml of hexane and get 98 mg (+), 1-dimethylheptyl) -2, bj-dioxyphenyl 1-6, b-dimethyl-2-nepinanone, which precipitates upon standing. Liquid. chromatographic
    5 on silica gel and get an additional amount of product. This product is identical to the product from example 3.
    PRI me R 9. (+) (1,1-Dimethylheptyl) -2, b-dioxyphenyl-b, b0-dimethyl-2-norpinan.
    119 mg of (+) - b, b-dimethyl-2,2-diaceroxy-3-norpinene and 118 mg of 5- (1,1-dimethylheptyl) -resorcinol are dissolved in 12.5 ml of dichloromethane at room temperature.
    5 and 0.05 mg boron trifluoride diethyl etherate is added. The mixture is stirred for 4 hours, then poured onto a mixture of ice and sodium bicarbonate and extracted with diethyl ether. Organic layer
    0 is dried over sodium sulfate, evaporated in vacuo and 250 mg of oil is obtained. This oil is triturated with 10 ml of hexane, from which the crystallized
    five
    60 mg (+) - 4 - {; 4- {1, l-dimethylheptyl) -2, b-dioxyphenyl-6,6-dimethyl-2-nopinanone.
    The product is identical to the product obtained in example 3.
    Example 10. {+) (l, l-Dimethylheptyl) -2, b-dioxyphenyl-b, b-dimethyl-2-norpinanon.
    119 mg of (+) - 6,6-dimethyl-2,3-diacetoxy-3-norpinene and 118 mg of 5 (1,1-dimethylheptyl) -resorcinol are dissolved in 12.5 ml of benzene at room temperature and 0 is added, 5 m diethyl trifluoride boron. The mixture is stirred at room temperature for 4 hours, treated and purified as described above, to obtain (+), (1,1-dimethylheptyl) -2, b-dioxyphenyl J-6, b-dimethyl-2-norpinano, identical to the product from example 3.
    Example 11. (+) - 4- (4-n-Pentyl-2, b-dioxyphenyl) -6,6-dimethyl-2-nopinanon.
    权利要求:
    Claims (3)
    [1]
    1.19 g of (-) - b, b-dimethyl-2,4-diacetoxy-2-norpinene and 0.9 g of 5-n-pentylresorcinol are dissolved in 50 ml of chloroform at room temperature and 0.95 is added. g para-toluenesulfonic acid monohydrate. The mixture was stirred at room temperature for 3 hours, then it was poured into 100 g of diethyl ether and washed twice with an aqueous solution of sodium bicarbonate and once with a saturated solution of sodium chloride in water. The organic layer is dried over sulfate and evaporated to dryness. The remaining oil is chromatographed on silica gel, eluted with chloroform, then with chloroform containing increasing amounts of methanol, up to 2%. The fractions containing the product are combined to give 1.08 g of (+) - 4- (4-n-pentyl-2, b- Dioxyphenide) -b, b-dimethyl-2-norpinanone td + 41.6 °. (with 1.0, CH, OH).
    Example 12. (+) - 4- {4-n-Pentyl-2, b-dioxyphenyl) -b, b-dimethyl-2-norpinanon.
    The procedure of Example 11 is repeated, starting from 1.19 g of (+) - b, b-dimethyl-2, 2.-diacetoxy-3-norepinene. 810 mg of (+) - 4- (4-n-pentyl-2, b-dirxyfeuyl) -b, 6-dimethyl-2-norpinanone are obtained, the analysis of which is identical to the analysis of the product from example 11.
    Example 13. (-) - 11, is-1-hydroxy-3- (1,1-dimethylgpptil) -b, b-tdimethyl-b, 6a, 7, B, 10,10a-hexahydro-9H-di6eH3o ( b, dj piran-9-he ..
    A solution of 372 mg (+) (1,1-dimethylheptyl) -2, b-dioxyphenyl-b, b-dimethyl-2-nrrpynanone, from example 3, in 25 ml of chloroform, containing 190 mg of p-toluenesulfonic acid monohydrate, is heated with - reflux with stirring for 24 hours. The reaction mixture is then cooled to room temperature, diluted with 25 ml of water and several
    extract once with 25 ml of diethyl ether. The ether extracts were combined, washed with 10% aqueous sodium bicarbonate solution and dried with water, the solvent was distilled off under reduced pressure, and 380 mg of product was obtained as white nt i ;. . The crude product thus obtained is chromatographed on a column packed with industrial silica gel, and elution is carried out with a 5% solution of diethyl ether in benzene. After removing the solvent from the corresponding fractions, 228 mg of (-) - CIS-1-OXI-3- (1,1-dimethylheptyl) -b, b-dimethyl-6, ba, 7,8,10,10- are obtained. hexahydro-9H-libenzo {ü, d) pyran-9-oca with so pl. 139.5-141 ° C, -1.0 in the dream 10.1; mass spectrum m / e: - calculated for C, l.CHOe 372.2664, found 372, 2665 Example 14. (-) - Cys-1-hydroxy-3- {1, 1 dimethylheptyl) -6,6-dimethyl -b, ba, 7,8,10,10l-hexahydro-9H-diben30 (b, d) pyran-9-one.
    The procedure is as described in Example 13. But the foamy residue obtained after evaporation of the solvent is chromatographed on silica gel and eluted with benzene and benzene, containing a small amount of diethyl ether. After evaporation of the fractions containing the product, 200 mg (-cis-1-hydroxy- 3- (1,1-dimethylheptyl) -§, b-dimethyl-b, ba, 7,8, 10, 10a-hexahydro-9H-dibene (b, d) pyran-9-one, identical to the product of example 13, and about 100 mg of the corresponding (-) - trans-hexahydrodibenzopyranone, identical to the product of example 18.
    Example g 15. (-) - Cys- and (- / - trans-1-hydroxy-3- (1,1-dimethylheptyl) -6, 6-dimethyl-b, ba, 7,8,10,10a-hexahydro -9H-dibenzo (b, d) pyran-9-ones.
    The procedure of Example 13 is repeated, but 25 ml of benzene is used as a solvent, and the reaction mixture is heated under reflux only for 4 hours. The yield after distilling off the solvent is 455 mg of a mixture of cis and trans isomers of about 1: 1. The crude product is chromatographed on silica gel, elution being carried out with benzene containing up to 3% ethyl acetate, and 140 mg are obtained for almost an hour of the iso7O trans trans isomer and 154 mg of the pot of pure cis isomer, analytically identical to the products of examples 18 and 13, respectively.
    Example 16. (-) - Cis- and (-) - trans-1-hydroxy-3- (1,1-dimethylheptyl-) -b, b-dimethyl-b, ba, 7,8,10,10a-hexahydro -9H-dibenzo (b, d pyran-9-ones.
    300 mg of (+) - 4-C4- (1,1 dimethylheptyl U2, b-dioxocphenylJ-6,6-dimethyl-2-norpinanone is dissolved in 25 ml of ethanol containing 25 ml of hydrochloric acid, the mixture is stirred
    at reflux temperature for 16 hours. The mixture is then cooled and purified according to a general method. from Example 13, a residual oil is obtained, which crystallizes upon addition of hexane. 20 mg of product is obtained, which is identified by thin-layer chromatography as an approximate mixture of 1: 1 cx: And trans isomers identical to the analytical products of examples 13 and 18, respectively.
    Example 17. (-) Cys- and (-} - trans-1-hydroxy-3 n-pentyl-b, 6-dimethyl-6, 6a, 7,8,10,1 Oa-hexahydro-9n-libeneo b, d) pyran-9-ones.
    632 mg of (+) - 4 (4-n-petyl-2, 6-dioxyphenyl) -6, 6-dimethyl-2-norP1-nanone from example 11 is dissolved with 25 ml of chloroform, 380 mg of p-toluenesulfonic acid monohydrate are added and the mixture is heated under reflux for 24 hours. Analysis of the reaction mixture shows complete conversion into almost equal parts of cis- and transhexahydrobenzo (b, d) pyranones, indicated by you. The reaction mixture is treated as in example 13 and receive products in the form of a foamy mixture.
    Example 18. (-) - Trans-1-hydroxy-3- (1,1-dimethylheptyl) -6,6-dimethyl-6, 6a, 7,8,10,10a-hexagidro-9H-dibenzo (b, d ) Piran-9-he.
    To a solution of 372 mg of (+) (1,1-dimethylheptyl) -2,6-dioxyphenyl-6,6-dimethyl-2-norpinanone in 25 ml of chloroform was added in one portion 1.0 ml of tin chloride. The reaction mixture is stirred at 25 ° C for 16 hours, then added to 50 g of ice. The aqueous reaction mixture is extracted several times with 25 ml of diethyl ether, the ether extracts are combined together, washed with 2N hydrochloric acid, then with 5% -HfciM aqueous sodium bicarbonate solution. Then the organic layer was washed with water, dried, the solvent was distilled off under reduced pressure, and 378 mg of product was obtained as a crude foam. This foam is then chromatographed on a silica gel column, and elution is carried out with benzene. After distilling off the solvent from the fractions in which, according to thin-layer chromatography, contains one component, 305 mg of {-) - trans-1-hydroxy-3- (1,1-dimethylheptyl) -6,6-dimethyl-6,6a is obtained, 7,8,10,10a-hexahydro-9H-dibe: zo (b, d) pyran-9-one., S (s 1.0, .CHCIj); mass spectrum calculated for C24HgbO 372.2664, found m / e 372.2667.
    After distilling off the solvent from the eluates, thin layer chromatography shows the presence of another component, namely 55 mg of (-) - cis-1-hydroxy-3- (1,1-dimethylheptyl) -6,6-dimethyl-6, 6a, 7.8 , 10,10a-hexahydro-9H-dibenzo-Cb, d) pyran-9-one (, 0, СНС1 ,,).
    Example 19. {-). Cis- and (-) - trais-1-hydroxy-3- (1,1-dimethylheptyl) -6, 6-dimethyl-6,6a, 7,8,10,10a-hexahydro AH-dibenzo (b, d) pyran-9-ones.
    10 mg of (+) (1,1-dimethylheptyl) -2,6-dioxyphenyl-6,6-dimethyl-2-norpinanone is treated with 1 ml of trifluoride triethyl efferate at reflux for 1 hour. Then the reaction mixture was poured onto ice and extracted with diethyl ether, the organic layer was washed with 5% aqueous sodium bicarbonate solution. The organic layer is dried, evaporated to dryness and analyzed by thin layer chromatography, which shows that it consists of a mixture of 1: 3 trans and cis isomers identical to the products of examples 18 and 13, respectively.
    Example 20. (-) - Cis-- and (-) - trans-1-hydroxy-3- (1,1-dimethylheptyl) -6, 6 dim teal-6.6a, 7.8, 10; 10a-hexahydro -H-dibenzo (b, d) pyran-9-ones.
    50 mg of the same norpinon, which is used in Example 19, is suspended in 5 ml of dichloromethane and 0.2 ml of tin chloride is added. The mixture is stirred for 20 hours at room temperature. After this, thin layer chromatography shows that norpinone is transformed into a mixture of 9: 1 trans and cis isomers, identical to the products of example 18 and 13, respectively.
    Example 21. (-) - Cis- and (-) - trans-1-hydroxy-3- (1,1-dimethylheptyl) -6, 6-dimethyl-6,6a, 7,8,10,10a-hexahydro 9H-dibenzo (b, d) pyran-9-one.
    The procedure of Example 20 is repeated, but benzene is used as the solvent and the mixture is first stirred for 2 hours at room temperature, then heated under reflux for 4 hours, then at room temperature for 16 hours. Thin layer chromatography shows 100% - conversion into a mixture of 9: 1 trans and cis isomers identical to the products of examples 18 and 13, respectively.
    Example 22. (-) - Cys- and (-) - trans-1-hydroxy-3- (1,1-dimethylheptyl) -6,6-dimethyl-6,6a, 7,8,10,10-hydroxy-hydro-9H- dibenzo (b, d) pyran-9-. - they are.
    50 mg of (+) (1,1-dimethylheptyl) -2, b-dioxyphenyl-b, 6-dimethyl-2-norpinanone is dissolved in 5 ml of dichloromethane and 0.2 ml of boron trifluoride diethyl etherate is added to the solution. The mixture is stirred for 1 hour at room temperature and erne is added in one portion of O, 2 ml of boron trifluoride diethyl etherate. The mixture is stirred for 4 hours, then it is analyzed by thin layer chromatography, which shows that norpinanone is converted to a mixture containing mainly the trans isomer identical to the product of example 18, and a very small amount of cis isomer identical to the product from example 13. Example 23. () -Cis- and (-) - trans-1-hydroxy Zn pentyl-6, b-dimethyl-6, 6a, 7,8,10,10a-hexahydro-9H-di benzo (b, d) pyrene -9-one 632 mg of (+) - 4 (4-n-pentyl-2, b-diociphenyl) -6, b-dimethyl-2-nopinanone are treated with 780 mg of tin chloride at room temperature for 6 h. Thin-layer chromatography shows that the initial The norpinonone is converted to a mixture of the above cistrans-hexahydrodibenzo (b, d} pyranone and that the trans isomer is the main product. The reaction mixture is worked up and purified as in example 13 and 622 mg of the mixed product is obtained as a foam. Example 24. { -) - Trans-1-hydroxy-3-n-pentyl-b, 6-dimethyl-b, 6a, 7,810, 10a-hexahydro-9H-dibenzo (b, d) -pyran-9-one. Each of the products of willows of examples 17 and 23 was separately dissolved in 25 ml of dichloromethane and 2 g of anhydrous aluminum chloride was added to each solution. The mixtures were stirred for 16 h at room temperature, then they were poured onto ice and diluted with diethyl ether. The organic layers of prog No. 1wat, first with water, then with 10% aqueous sodium bicarbonate solution, dried, evaporated in vacuo, and in each case, about 560 mg of an oily product are obtained. These products are combined and chromatographed on silica gel, elution is carried out with a mixture of 1: 1 hexane ethyl ether. The fractions containing the product were combined, evaporated to dryness, and 333 mg of product were obtained, which was dissolved in diethyl ether and washed with 1N sodium hydroxide solution for 1 hour. The organic layer was then dried over sodium sulfate, evaporated in a vacuum and 297 mg were obtained on the basis of pure (-) - trans-1-hydroxy-3-n-pen tyl-6, b-dimethyl-b, 6a, 7,8,10, sagidro-9H-dibenzo (b, d) pyran-9- she is. , 30 (with 1.0 - sleep Ij). In the following example, the preparation of hexahydrobenzopyr is shown: in one stage, the ions of norpinenes of the formula In this example, not a preferred embodiment of the invention is shown, but only a possible application of the present invention is shown: R and m 25 p. {-) - Trans-1-hydroxy-3- (1,1-dimethylheptyl) -b, 6- dimethyl-6, ba, 7,8,10,10a-hexahydro-9H-dibenzo (b, djpyran-9-one. A mixture of 2.38 g of (-) 6,6-dimethyl-2,4-diacetoxy-2- norpinene and 2.76 g of 5- (1,1-dimethylheptyl) -resorcinol are dissolved in 50 ml of dichloromethane containing 10.2 g of boron trifluoride diethyl etherate, cooled to 0 ° C in an ice bath and stirred for 1 h. Then the reaction mixture is heated before and stirred for another 12 hours. Then the reaction mixture is heated. The mixture is poured onto 25 g of ice and the resulting aqueous mixture is extracted with diethyl ether. The organic layer is separated, washed with 10% aqueous sodium bicarbonate solution, dried, the solvent is distilled off under reduced pressure and 4.1 g of brown oil are obtained. The oil thus obtained purified by chromatography on a column of silica gel, with elution being carried out with benzene.The appropriate fractions containing the desired products by thin layer chromatography are combined, the solvent is distilled off and 1.06 g of (-) - trans-1-hydroxy-3- (1, one- imetilgeptil) -b, 6-dimethyl-b, ba, 7,8,10,10ageksagidro-9H-dibenzo (b, d) pyran-9-one as a colorless oil. oL, - 47.5 "(, 0, SNAe). According to the above procedure, (+) -b, b-dimethyl-2,2-diacetoxy-3-norpinene is reacted with 5- (1,1-dimethylheptyl) -resorcinol in the presence of boron trifluoride diethyl etherate and {-) - trans-1 is obtained -oxy-3- (1,1-dimethylheptyl) -6,6-dimethyl-b, 6a, 7.8, 10.10a-hexahydro-9H-dibenzo (b, d) pyran-9-one. The following procedure shows the conversion of cis compounds of the formula T into a trans compound. Method 1. (-) - trans-1-hydroxy-3- (1,1-dimethylheptyl) -b, 6-dimethyl-6, 6a, 7,8,10,10a-hexahydro-9H-di6eH3otb, d) pyran -9-he A solution of 77 mg (.) - cis-1-hydroxy-3- (1,1-dimethylheptyl) -6,6-dimethyl-b, ba, 7,8,10,10a-hexahydro-9H-dibenzo {b, djpyran -9-one in 5 ml of dichloromethane containing 77 mg of aluminum chloride is stirred at 25 ° C for 4 hours. Then the reaction mixture is diluted with 20 g of ice and the resulting aqueous mixture is extracted with diethyl ether. The ether extracts were combined, washed with 2N hydrochloric acid and 10% aqueous sodium bicarbonate solution, then washed with water, dried, the solvent was distilled off under reduced pressure, and 75 mg of product was obtained as an oil. The oil thus obtained is chromatographed on a thick silica gel plate. Elution of the base band with 20% ethyl acetate in benzene and evaporation of the solvent gives 54 mg of (-) - trans-1-hydroxy-3- (1,1-dimethylheptyl) -6,6-dimethyl-6,6a, 7 8, 10, 10a-hexahydro-9H-dibenea (b, th pyran-9-one.; A (, 2.o 53.8., 0 sns.). Claims 1. Method of obtaining the optical isomer L-hydroxy-3- substituted 6,6-dimethyl-6, ba, 7,8,10,10a-hexahydry-9H-dibenzo (b, 1) pyran-9-one of the general formula I, where R is alkyl C, -. / and hydrogen atoms , and the Yua positions are in: the cis or trans conformation, about t and h with the fact that the optically active norpinane compound of the formula II BUT-L g de R has this value, it is reacted with an acid in an organic pacTBOtjitel medium, at a temperature from to the boiling point of the reaction medium.
    [2]
    2. Method POP 1, characterized in that protic acid, p-toluenesulfonic acid or Lewis acid is used as the acid.
    [3]
    3. The method according to claim 1, characterized in that sloroform or benzene is used as an organic solvent. Sources of information taken into account when examining Il. K.E. FahrenhoTtz, M.LurJe, R.W, Kierstead, Total Synthests of di L.9 -Tetrahydrocannabi ol, ACS, 1966, 83, 2079.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU786898A3|1980-12-07|Method of preparing optical isomer of 1-hydroxy-3-substituted 6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9h-dibenzo | pyran-9-one
    Pearce et al.1976|Synthesis and absolute configuration of multistriatin
    EP0004753B1|1982-05-26|Preparation of tetrahydrobenzoxocins and cis-hexahydrodibenzopyranones
    Keck et al.1986|A highly convergent total synthesis of |-compactin
    Johnson et al.1984|Asymmetric Synthesis via Acetal Templates. 10. Aldol-Type Reactions. Preparation of a Nonacetic Acid Intermediate
    Yadav et al.2008|Stereoconvergent synthesis of C1–C17 and C18–C25 fragments of bafilomycin A1
    Acharyya et al.2018|Asymmetric total synthesis of naturally occurring spirocyclic tetranorsesquiterpenoid lanceolactone A
    Harmata et al.1995|Intramolecular [4+ 3] cycloadditions. Studies of relative asymmetric induction
    EP0183132B1|1989-10-18|A process for the preparation of hmg-coa reductase inhibitors and intermediate compounds employed therein
    Nakatani et al.1992|Synthetic studies on the compounds related to neocarzinostatin chromophore. 2. Synthesis of the open-chain |-and |-dienediyne systems and its application to the synthesis of a strain-released cyclic analogue
    US4140701A|1979-02-20|2,6-Methano-2H-1-benzoxocins
    Tate et al.2006|A highly enantioselective total synthesis of |-goniodiol
    Kallmerten et al.1985|A short, stereocontrolled synthesis of avenaciolide
    SU649311A3|1979-02-25|Method of obtaining alkyl-derivatives of prostanic acid
    Beszant et al.2002|Enantioselective synthesis of both enantiomers of γ-ionone, γ-damascone, karahana lactone and karahana ether
    Vanaltena et al.1989|A study of the terpenoids of the sponge Euryspongia sp
    Inanaga et al.1986|Total synthesis of neomethynolide
    Tsuboi et al.1987|Reinvestigation of Base-Catalyzed Condensation of Ethyl α, α-Dichloroacetoacetate with Aldehydes. A New Synthesis of |-Disparlure
    Niwa et al.1976|Biogenetic Model Reactions of Epoxygermacrones
    Raffaelli et al.2006|Asymmetric synthesis, stereochemistry and rearrangement reactions of naturally occurring 7′-hydroxylignano-9, 9′-lactones
    Henry et al.2001|A short synthesis of 5-methoxy-2, 2-dimethyl-2H-1-benzopyran-6-propanoic acid methyl ester
    SU988817A1|1983-01-15|Process for producing tetrahydrofurans
    Dias et al.2005|Short synthesis of a new cyclopentene-1, 3-dione derivative isolated from Piper carniconnectivum
    Watanabe et al.1982|Synthesis of 3-Acylfurans Using 3-| propanal Dimethyl Acetal as a New Synthon. Syntheses of Ipomeanine and Isoegomaketone
    Vakalopoulos et al.2002|Structural and Stereochemical Diversity from |‐2, 2‐Dimethyl‐8‐oxabicyclo [3.2. 1] oct‐6‐en‐3‐one− Application to the Synthesis of Polyketide Segments of Natural Products
    同族专利:
    公开号 | 公开日
    PL104432B1|1979-08-31|
    SU1128829A3|1984-12-07|
    SE434510B|1984-07-30|
    AT356103B|1980-04-10|
    DD140455A5|1980-03-05|
    IE45247B1|1982-07-14|
    IL52427D0|1977-08-31|
    JPS5912654B2|1984-03-24|
    HU177308B|1981-09-28|
    FR2370742B1|1980-12-26|
    SE8005314L|1980-07-22|
    PT66746B|1978-11-27|
    ES460388A1|1978-04-01|
    IL52427A|1981-10-30|
    FR2370742A1|1978-06-09|
    IL60590D0|1980-09-16|
    CA1101875A|1981-05-26|
    ES460387A1|1978-04-01|
    RO78780A|1982-04-12|
    BG28411A4|1980-04-15|
    JPS5925792B2|1984-06-21|
    BG28061A3|1980-02-25|
    PH14708A|1981-11-13|
    BE856413A|1978-01-04|
    DD134350A5|1979-02-21|
    PL199362A1|1978-05-22|
    ES460389A1|1978-04-16|
    NL7707467A|1978-05-12|
    JPS5865244A|1983-04-18|
    DE2729859A1|1978-05-11|
    PH13827A|1980-10-07|
    AU2668477A|1979-01-04|
    GB1584182A|1981-02-11|
    PL104356B1|1979-08-31|
    GB1584181A|1981-02-11|
    SE428020B|1983-05-30|
    AU509355B2|1980-05-08|
    MX5172E|1983-04-18|
    SE7707633L|1978-05-11|
    CH632481A5|1982-10-15|
    NZ184526A|1979-03-16|
    PT66746A|1977-07-01|
    IL60589D0|1980-09-16|
    DE2760005C2|1984-04-26|
    HU183286B|1984-04-28|
    JPS5359670A|1978-05-29|
    DE2760006C2|1985-07-04|
    SE8005316L|1980-07-22|
    ATA483677A|1979-09-15|
    US4102902A|1978-07-25|
    DK301477A|1978-05-11|
    IE45247L|1978-05-10|
    ZA773960B|1979-02-28|
    CH632506A5|1982-10-15|
    CS196376B2|1980-03-31|
    YU163677A|1982-10-31|
    GR66417B|1981-03-20|
    PH13890A|1980-10-27|
    DE2729859C2|1984-08-23|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3856820A|1973-07-18|1974-12-24|Smithkline Corp|2-AMINOMETHYL DIBENZO PYRANS|
    US3856822A|1973-07-18|1974-12-24|Smithkline Corp|3-alkenyl dibenzo pyrans|
    US3856821A|1973-07-18|1974-12-24|Smithkline Corp|ALKOXY DIBENZO PYRANS|
    US3928598A|1973-11-05|1975-12-23|Lilly Co Eli|Hexahydro-dibenzo{8 b,d{9 pyran-9-ones as an anti-anxiety drug|IL55274A|1978-08-02|1982-08-31|Yissum Res Dev Co|4-phenyl)substituted 2-pinen-10-ol and pinane derivatives,their preparation and pharmaceutical compositions comprising them|
    WO1987001698A2|1985-09-20|1987-03-26|The Upjohn Company|1,4-naphthalenediol and 1,4-hydroquinone derivatives|
    US4939169A|1985-09-20|1990-07-03|The Upjohn Company|1,4-naphthalenediol and 1,4-hydroquinone derivatives|
    IL80411A|1986-10-24|1991-08-16|Raphael Mechoulam|Preparation of dibenzopyranol derivatives and pharmaceutical compositions containing them|
    JPH0315035A|1989-03-03|1991-01-23|Konica Corp|Camera|
    JP2577671B2|1990-06-11|1997-02-05|高砂熱学工業株式会社|Vaporization type precision humidifier|
    CA2340445A1|1998-05-04|1999-11-11|The University Of Connecticut|Novel analgesic and immunomodulatory cannabinoids|
    US7897598B2|1998-06-09|2011-03-01|Alexandros Makriyannis|Inhibitors of the anandamide transporter|
    US7589220B2|1998-06-09|2009-09-15|University Of Connecticut|Inhibitors of the anandamide transporter|
    US7276613B1|1998-11-24|2007-10-02|University Of Connecticut|Retro-anandamides, high affinity and stability cannabinoid receptor ligands|
    US7161016B1|1998-11-24|2007-01-09|University Of Connecticut|Cannabimimetic lipid amides as useful medications|
    US7741365B2|1999-10-18|2010-06-22|University Of Connecticut|Peripheral cannabinoid receptorselective ligands|
    US6900236B1|1999-10-18|2005-05-31|University Of Connecticut|Cannabimimetic indole derivatives|
    DE60033545T2|1999-10-18|2007-10-31|The University Of Connecticut, Farmington|NEW BICYCLIC CANNABINOID AGONISTS FOR THE CANNABINOID RECEPTOR|
    US7119108B1|1999-10-18|2006-10-10|University Of Connecticut|Pyrazole derivatives as cannabinoid receptor antagonists|
    US8084467B2|1999-10-18|2011-12-27|University Of Connecticut|Pyrazole derivatives as cannabinoid receptor antagonists|
    US6943266B1|1999-10-18|2005-09-13|University Of Connecticut|Bicyclic cannabinoid agonists for the cannabinoid receptor|
    US6995187B1|1999-10-18|2006-02-07|University Of Connecticut|Peripheral cannabinoid receptorselective ligands|
    CA2435409A1|2001-01-26|2002-08-01|University Of Connecticut|Novel cannabimimetic ligands|
    EP1363632B1|2001-01-29|2010-08-25|The University of Connecticut|Receptor selective cannabimimetic aminoalkylindoles|
    WO2003005960A2|2001-07-13|2003-01-23|University Of Connecticut|Novel bicyclic and tricyclic cannabinoids|
    US7393842B2|2001-08-31|2008-07-01|University Of Connecticut|Pyrazole analogs acting on cannabinoid receptors|
    US7666867B2|2001-10-26|2010-02-23|University Of Connecticut|Heteroindanes: a new class of potent cannabimimetic ligands|
    CA2483072A1|2002-04-25|2003-11-06|Virginia Commonwealth University|Cannabinoids|
    CN1678303A|2002-08-23|2005-10-05|康涅狄格大学|Keto cannabinoids with therapeutic indications|
    WO2007041167A2|2005-09-29|2007-04-12|Amr Technology, Inc.|Process for production of delta-9-tetrahydrocannabinol|
    US9763894B2|2006-12-05|2017-09-19|Virginia Commonwealth University|Inflammation therapy|
    PL222532B1|2012-04-05|2016-08-31|Akademia Morska W Szczecinie|Method and system for diagnosing the injection system of compression-ignition engines, especially marine engines|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US05/740,502|US4102902A|1976-11-10|1976-11-10|Stereoselective preparation of hexahydro dibenzopyranones and intermediates therefor|
    [返回顶部]