SQ 28668

合成路线:The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III),which is reduced with H2 over Pd/C,yielding the epoxyperhydrophthalic anhydride (IV).Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V),which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol.The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX),which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH,yielding the cis-5-heptenoic acid methyl ester (XI).The oxidation of the primary alcohol group of (XI) with pyridinium chlorochromate (PCC) in dichloromethane affords the aldehyde (XII),which is finally reductocondensed with 4-phenylsemicarbazide (XIII) by means of NaBH3CN and hydrolyzed with LiOH to furnish the target semicarbazide.

合成路线:The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III),which is reduced with H2 over Pd/C,yielding the epoxyperhydrophthalic anhydride (IV).Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V),which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol.The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX),which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH,yielding the cis-5-heptenoic acid methyl ester (XI).The oxidation of the primary alcohol group of (XI) with pyridinium chlorochromate (PCC) in dichloromethane affords the aldehyde (XII),which is condensed with dimethyl 2-oxobutylphosphonate (XIII) and NaH,providing the pentenone (XIV).Finally,the ketonic group of (XIV) is reduced with NaBH4/CeCl3,and the resulting ester hydrolyzed with LiOH to furnish the target hydroxyacid as a diastereomeric mixture that is separated by conventional methods.

合成路线:The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III),which is reduced with H2 over Pd/C,yielding the epoxyperhydrophthalic anhydride (IV).Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V),which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol.The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX),which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH,yielding the cis-5-heptenoic acid methyl ester (XI).The sulfonation of the primary alcohol group of (XI) with TsOH affords the tosylate (XII),which is condensed with potassium phthalimide (XII) to provide the phthalimido derivative (XIV).The treatment of (XIV) with hydrazine gives the aminomethyl compound (XV),which is finally condensed with N-(heptanoyl)glycine (XVI) by means of CDI and hydrolyzed with LiOH to afford the target glycinamide compound.

参考文献标题:Aza-substituted omega side chain modification of 7-oxabicyclo[2.2.1]heptane TxA2 receptor antagonists: Structure-activity relationships
文献作者:Haslanger,M.F.; Greenberg,M.J.; Ogletree,M.L.; Nakane,M.; Garber,D.P.; Harris,D.N.; Reid,J.C.
参考来源:Advances in Prostaglandin,Thromboxane and Leukotriene Research,vol.15; O.Hayaishi and S.Yamamoto (Eds.).Raven Press: New York 1985,291-293


合成路线:The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III),which is reduced with H2 over Pd/C,yielding the epoxyperhydrophthalic anhydride (IV).Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V),which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol.The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX),which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH,yielding the cis-5-heptenoic acid methyl ester (XI).The oxidation of the primary alcohol group of (XI) with pyridinium chlorochromate (PCC) in dichloromethane affords the aldehyde (XII),which is finally reductocondensed with 4-phenylsemicarbazide (XIII) by means of NaBH3CN and hydrolyzed with LiOH to furnish the target semicarbazide.

合成路线:The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III),which is reduced with H2 over Pd/C,yielding the epoxyperhydrophthalic anhydride (IV).Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V),which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol.The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX),which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH,yielding the cis-5-heptenoic acid methyl ester (XI).The oxidation of the primary alcohol group of (XI) with pyridinium chlorochromate (PCC) in dichloromethane affords the aldehyde (XII),which is condensed with dimethyl 2-oxobutylphosphonate (XIII) and NaH,providing the pentenone (XIV).Finally,the ketonic group of (XIV) is reduced with NaBH4/CeCl3,and the resulting ester hydrolyzed with LiOH to furnish the target hydroxyacid as a diastereomeric mixture that is separated by conventional methods.

合成路线:The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III),which is reduced with H2 over Pd/C,yielding the epoxyperhydrophthalic anhydride (IV).Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V),which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol.The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX),which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH,yielding the cis-5-heptenoic acid methyl ester (XI).The sulfonation of the primary alcohol group of (XI) with TsOH affords the tosylate (XII),which is condensed with potassium phthalimide (XII) to provide the phthalimido derivative (XIV).The treatment of (XIV) with hydrazine gives the aminomethyl compound (XV),which is finally condensed with N-(heptanoyl)glycine (XVI) by means of CDI and hydrolyzed with LiOH to afford the target glycinamide compound.

参考文献标题:9,11-Epoxy-9-homo-14-oxaprosta-5-enoic acid derivatives.Novel inhibitors of fatty acid cyclooxygenase
文献作者:Haslanger,M.F.; Han,W.-C.; Ogletree,M.L.; Hall,S.E.; Harris,D.N.
参考来源:J Med Chem 1986,292335-2347


合成路线:The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III),which is reduced with H2 over Pd/C,yielding the epoxyperhydrophthalic anhydride (IV).Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V),which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol.The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX),which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH,yielding the cis-5-heptenoic acid methyl ester (XI).The oxidation of the primary alcohol group of (XI) with pyridinium chlorochromate (PCC) in dichloromethane affords the aldehyde (XII),which is finally reductocondensed with 4-phenylsemicarbazide (XIII) by means of NaBH3CN and hydrolyzed with LiOH to furnish the target semicarbazide.

合成路线:The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III),which is reduced with H2 over Pd/C,yielding the epoxyperhydrophthalic anhydride (IV).Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V),which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol.The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX),which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH,yielding the cis-5-heptenoic acid methyl ester (XI).The oxidation of the primary alcohol group of (XI) with pyridinium chlorochromate (PCC) in dichloromethane affords the aldehyde (XII),which is condensed with dimethyl 2-oxobutylphosphonate (XIII) and NaH,providing the pentenone (XIV).Finally,the ketonic group of (XIV) is reduced with NaBH4/CeCl3,and the resulting ester hydrolyzed with LiOH to furnish the target hydroxyacid as a diastereomeric mixture that is separated by conventional methods.

合成路线:The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III),which is reduced with H2 over Pd/C,yielding the epoxyperhydrophthalic anhydride (IV).Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V),which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol.The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX),which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH,yielding the cis-5-heptenoic acid methyl ester (XI).The sulfonation of the primary alcohol group of (XI) with TsOH affords the tosylate (XII),which is condensed with potassium phthalimide (XII) to provide the phthalimido derivative (XIV).The treatment of (XIV) with hydrazine gives the aminomethyl compound (XV),which is finally condensed with N-(heptanoyl)glycine (XVI) by means of CDI and hydrolyzed with LiOH to afford the target glycinamide compound.
参考文献标题:7-Oxabicycloheptane analogs: modulators of the arachidonate cascade
文献作者:Hedberg,A.; Hall,S.E.; Harris,D.N.; Ogletree,M.L.
参考来源:Drugs Fut 1988,13(2),153