合成路线:The hydrogenation of ethyl 3-(2-furyl)acrylate (I) with H2 over Raney-Ni in ethanol gives ethyl 3-(2-furyl)propionate (II),which oxidative methoxylation with Br2 in methanol affords ethyl 3-(2,5-dimethoxy-2,5-dihydro-2-furyl)propionate (III).The partial reduction of (III) with diisobutylaluminum hydride in toluene yields the substituted propionaldehyde (IV),which by a Wittig condensation with 4-carboxybutyl triphenylphosphonium bromide by means of NaH in DMSO gives 8-(2,5-dimethoxy-2,5-dihydro-2-furyl)-5-octenoic acid (VI).The hydrolytic ring opening of (VI),followed by an aldol cyclization in refluxing dioxane - water by means of sodium acetate - NaH2PO4 - hydroquinone affords 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoic acid (VII),which is isomerized by treatment with H2SO4 yielding 7-(5-oxo-3-hydroxycyclopenten-1-yl)-5-heptenoic acid (VIII).Methylation and esterification of (VIII) with H2SO4/refluxing methanol gives the methoxy methyl ester (IX),which by reaction with 2-mercaptoethanol (A) and sodium methoxide in methanol is converted into methyl 7-[5-oxo-3-(2-hydroxyethylthio)cyclopenten-1-yl]-5-heptenoate (X).The methylation of acid (VI) with NaH and methyl iodide gives the corresponding methyl ester (XIV),which is submitted to a hydrolytic ring opening and aldol cyclization as before to afford methyl 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoate (XV).The silylation of (XV) with trimethylchlorosilane and hexamethyldisilazane as usual yields the corresponding trimethylsilyloxy derivative (XVI),which is treated with 2-mercaptoethanol (A) and sodium methoxide to give the isomerized compound (X).
合成路线:The protection of the free hydroxy group of (X) with trimethylchlorosilane and hexamethyldisilazane in pyridine gives the trimethylsilyl derivative (XI),which is condensed with [3-(triphenylmethoxy)-1-octenyl](pentenyl)lithiocuprate (XII) in HMPT-ether to afford 11-deoxy-11alpha-(2-trimethyl-silyloxyethylthio)-15-triphenylmethoxy-PGE2 methyl ester (XIII).Finally,this compound is deprotected by treatment with acetic acid in THF.The lithium cuprate (XII) is prepared as follows:Hydrogen iodide addition to 3-triphenylmethoxy-1-octyne (XVII) gives 1-iodo-3-triphenylmethoxy-1-octene (XVIII),which is condensed with copper 1-pentyne (B) and butyllithium in ether.
参考文献标题:DHET-PGE2
文献作者:Hillier,K.; Serradell,M.N.; Blancafort,P.; Castar,J.
参考来源:Drugs Fut 1982,7(4),241
合成路线:The hydrogenation of ethyl 3-(2-furyl)acrylate (I) with H2 over Raney-Ni in ethanol gives ethyl 3-(2-furyl)propionate (II),which oxidative methoxylation with Br2 in methanol affords ethyl 3-(2,5-dimethoxy-2,5-dihydro-2-furyl)propionate (III).The partial reduction of (III) with diisobutylaluminum hydride in toluene yields the substituted propionaldehyde (IV),which by a Wittig condensation with 4-carboxybutyl triphenylphosphonium bromide by means of NaH in DMSO gives 8-(2,5-dimethoxy-2,5-dihydro-2-furyl)-5-octenoic acid (VI).The hydrolytic ring opening of (VI),followed by an aldol cyclization in refluxing dioxane - water by means of sodium acetate - NaH2PO4 - hydroquinone affords 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoic acid (VII),which is isomerized by treatment with H2SO4 yielding 7-(5-oxo-3-hydroxycyclopenten-1-yl)-5-heptenoic acid (VIII).Methylation and esterification of (VIII) with H2SO4/refluxing methanol gives the methoxy methyl ester (IX),which by reaction with 2-mercaptoethanol (A) and sodium methoxide in methanol is converted into methyl 7-[5-oxo-3-(2-hydroxyethylthio)cyclopenten-1-yl]-5-heptenoate (X).The methylation of acid (VI) with NaH and methyl iodide gives the corresponding methyl ester (XIV),which is submitted to a hydrolytic ring opening and aldol cyclization as before to afford methyl 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoate (XV).The silylation of (XV) with trimethylchlorosilane and hexamethyldisilazane as usual yields the corresponding trimethylsilyloxy derivative (XVI),which is treated with 2-mercaptoethanol (A) and sodium methoxide to give the isomerized compound (X).
合成路线:The protection of the free hydroxy group of (X) with trimethylchlorosilane and hexamethyldisilazane in pyridine gives the trimethylsilyl derivative (XI),which is condensed with [3-(triphenylmethoxy)-1-octenyl](pentenyl)lithiocuprate (XII) in HMPT-ether to afford 11-deoxy-11alpha-(2-trimethyl-silyloxyethylthio)-15-triphenylmethoxy-PGE2 methyl ester (XIII).Finally,this compound is deprotected by treatment with acetic acid in THF.The lithium cuprate (XII) is prepared as follows:Hydrogen iodide addition to 3-triphenylmethoxy-1-octyne (XVII) gives 1-iodo-3-triphenylmethoxy-1-octene (XVIII),which is condensed with copper 1-pentyne (B) and butyllithium in ether.
参考文献标题:Prostaglandins and congeners.22.Synthesis of 11-substituted derivatives of 11-deoxyprostaglandins E1 and E2.Potential bronchodilators
文献作者:Floyd,M.; Schaub,R.E.; Siuta,G.J.; Skotnicki,J.S.; Grudzinskas,C.V.; Weiss,M.J.; Dessy,F.; VanHumbeeck,L.
参考来源:J Med Chem 1980,23(8),903-913
合成路线:The hydrogenation of ethyl 3-(2-furyl)acrylate (I) with H2 over Raney-Ni in ethanol gives ethyl 3-(2-furyl)propionate (II),which oxidative methoxylation with Br2 in methanol affords ethyl 3-(2,5-dimethoxy-2,5-dihydro-2-furyl)propionate (III).The partial reduction of (III) with diisobutylaluminum hydride in toluene yields the substituted propionaldehyde (IV),which by a Wittig condensation with 4-carboxybutyl triphenylphosphonium bromide by means of NaH in DMSO gives 8-(2,5-dimethoxy-2,5-dihydro-2-furyl)-5-octenoic acid (VI).The hydrolytic ring opening of (VI),followed by an aldol cyclization in refluxing dioxane - water by means of sodium acetate - NaH2PO4 - hydroquinone affords 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoic acid (VII),which is isomerized by treatment with H2SO4 yielding 7-(5-oxo-3-hydroxycyclopenten-1-yl)-5-heptenoic acid (VIII).Methylation and esterification of (VIII) with H2SO4/refluxing methanol gives the methoxy methyl ester (IX),which by reaction with 2-mercaptoethanol (A) and sodium methoxide in methanol is converted into methyl 7-[5-oxo-3-(2-hydroxyethylthio)cyclopenten-1-yl]-5-heptenoate (X).The methylation of acid (VI) with NaH and methyl iodide gives the corresponding methyl ester (XIV),which is submitted to a hydrolytic ring opening and aldol cyclization as before to afford methyl 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoate (XV).The silylation of (XV) with trimethylchlorosilane and hexamethyldisilazane as usual yields the corresponding trimethylsilyloxy derivative (XVI),which is treated with 2-mercaptoethanol (A) and sodium methoxide to give the isomerized compound (X).
参考文献标题:Prostaglandins and congeners.18.Synthesis of cyclopentenolone precursors to prostaglandins from 2,5-dihydro-2,5-dimethoxyfurans
文献作者:Floyd,M.B.
参考来源:J Org Chem 1978,43(9),1641-43
产品链接: CAS No. 74412-44-5››