Beraprost sodium, RU-55100, ML-1229(free acid), ML-1129, TRK-100, Beraprost, Dorner, Procylin

合成路线:The reaction of 7-bromo-3a,8b-cis-3a,8b dihydro-3H-5-cyclopenta[b]benzofurancarboxylic acid (I) with trioxane and H2SO4,followed by methylation with diazomethane and debromination with H2 over Pd/C,gives the hydroxymethyl compound (II),which is protected with 1,1-diethoxyethane and p-toluenesulfonic acid to give the protected ester (III).Reduction of the ester (III) with LiAlH4 in THF affords the corresponding hydroxymethyl compound (IV),which by reaction with SOCl2 in DMF is converted to the chlorometnyl derivative (VI).The condensation of (V) with beta-propiolactone (VI) by means of Mg in TFH gives the phenylbutyric acid (VII),which by methylation with diazomethane and deprotection with HCl in metnanol yields the dihydroxyester (VIII).Selective acetylation of (VIII) by reaction with trimethyl-tert-butylchlorosilane,then with acetic anhydride and final desilylation with acetic acid affords methyl 4-(2alpha-acetoxy-1-hydroxymethyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuranyl)butyrate (IX),which is oxidized with DMSO.dicyclohexylcarbodiimide (DCC) and trifluoroacetic acid to the corresponding aldehyde (X).The Wittig condensation of (X) with dimethyl 3-methyl-2-oxohept-5-yn-1-yl phosphonate (XI) by means of NaH in DMF affords 11,15-dideoxy-11-acetoxy-16-methyl-15-oxo-18,19-tetradehydro-5,6,7-trinor-4,8-inter-m-phenylene-prostaglandin I2 methyl ester (XII),vvhich is reduced with cerium chloride and NaBH4 in methanol to the corresponding 15-hydroxy compound (XIII).Finally,this compound is deacetylated and saponified as usual.

参考文献标题:Preparation of 5,6,7-trinor-4,8-inter-m-phenylene pgi2derivative
文献作者:Matsumoto,K.; Nagase,H.; Ohno,K.(Toray Industries,Inc.)
参考来源:JP 1984134787


合成路线:The reaction of 7-bromo-3a,8b-cis-3a,8b dihydro-3H-5-cyclopenta[b]benzofurancarboxylic acid (I) with trioxane and H2SO4,followed by methylation with diazomethane and debromination with H2 over Pd/C,gives the hydroxymethyl compound (II),which is protected with 1,1-diethoxyethane and p-toluenesulfonic acid to give the protected ester (III).Reduction of the ester (III) with LiAlH4 in THF affords the corresponding hydroxymethyl compound (IV),which by reaction with SOCl2 in DMF is converted to the chlorometnyl derivative (VI).The condensation of (V) with beta-propiolactone (VI) by means of Mg in TFH gives the phenylbutyric acid (VII),which by methylation with diazomethane and deprotection with HCl in metnanol yields the dihydroxyester (VIII).Selective acetylation of (VIII) by reaction with trimethyl-tert-butylchlorosilane,then with acetic anhydride and final desilylation with acetic acid affords methyl 4-(2alpha-acetoxy-1-hydroxymethyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuranyl)butyrate (IX),which is oxidized with DMSO.dicyclohexylcarbodiimide (DCC) and trifluoroacetic acid to the corresponding aldehyde (X).The Wittig condensation of (X) with dimethyl 3-methyl-2-oxohept-5-yn-1-yl phosphonate (XI) by means of NaH in DMF affords 11,15-dideoxy-11-acetoxy-16-methyl-15-oxo-18,19-tetradehydro-5,6,7-trinor-4,8-inter-m-phenylene-prostaglandin I2 methyl ester (XII),vvhich is reduced with cerium chloride and NaBH4 in methanol to the corresponding 15-hydroxy compound (XIII).Finally,this compound is deacetylated and saponified as usual.
参考文献标题:TRK-100
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1986,11(11),956


产品链接: CAS No. 88475-69-8››

产品链接: CAS No.88430-50-6››