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【结 构 式】

【分子编号】43991

【品名】(5aS,9aS)-9a-(hydroxymethyl)-4-methoxy-5a,6,7,9a-tetrahydrodibenzo[b,d]furan-1-carbaldehyde

【CA登记号】

【 分 子 式 】C15H16O4

【 分 子 量 】260.28964

【元素组成】C 69.22% H 6.2% O 24.59%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

The enantioselective condensation of 2-bromovanillin (I) with cyclohexenecarboxylate (II) by means of the chiral phosphine ligand (III) gives the chiral aryl ether (IV), which is reduced with DIBAL to yield the diol (V). The protection of (V) with Tbdms-OTf affords the bis silyl ether (VI), which is cyclized by means of Pd(OAc)2 to furnish the tetrahydrodibenzofuran (VII). The deprotection of (VII) with TBAF gives the diol (VIII), which is chemoselectively oxidized with MnO2 to yield the hydroxyaldehyde (IX). The reductocondensation of (IX) with methylamine and NaBH3CN affords the secondary amine (X), which is protected with Boc2O, providing the carbamate (XI). The oxidation of (XI) with DMP gives the aldehyde (XII), which is condensed with the phosphonium bromide (XIII) and NaHMDS, yielding the vinyl ether (XIV). The deprotection and cyclization of (XIV) by means of TFA affords the seven-member ring hemiaminal (XV), which is reduced with NaBH3CN to provide deoxygalanthamine (XVI). The epoxidation of (XVI) with dimethyldioxirane (DMDO) and TsOH furnishes the epoxide (XVII), which is regioselectively opened with diphenyl diselenide and NaBH4 to give the alpha-hydroxy selenide (XVIII). Elimination of the selenide group of (XVIII) by oxidation with NaIO4 at 80 C yielded isogalanthamine (XIX), which is finally isomerized to the target compound by treatment with Osborn's rhenium catalyst (Ph3SiO-ReO3).

1 Trost, B.M.; Toste, F.D.; Enantioselective total synthesis of (-)-galanthamine. J Am Chem Soc 2000, 122, 45, 11262.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 26230 2-bromo-3-hydroxy-4-methoxybenzaldehyde C8H7BrO3 详情 详情
(II) 43984 methyl 6-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-1-cyclohexene-1-carboxylate C11H13Cl3O5 详情 详情
(III) 43985 2-(diphenylphosphino)-N-((1S,2S)-2-[[2-(diphenylphosphino)benzoyl]amino]-1,2-diphenylethyl)benzamide C52H42N2O2P2 详情 详情
(IV) 43986 methyl (6S)-6-(2-bromo-3-formyl-6-methoxyphenoxy)-1-cyclohexene-1-carboxylate C16H17BrO5 详情 详情
(V) 43987 [(6S)-6-[2-bromo-3-(hydroxymethyl)-6-methoxyphenoxy]-1-cyclohexen-1-yl]methanol C15H19BrO4 详情 详情
(VI) 43988 3-bromo-4-([[tert-butyl(dimethyl)silyl]oxy]methyl)-2-[[(1S)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-2-cyclohexen-1-yl]oxy]phenyl methyl ether; ([(6S)-6-[2-bromo-3-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6-methoxyphenoxy]-1-cyclohexen-1-yl]methoxy)(tert-butyl)dimethylsilane C27H47BrO4Si2 详情 详情
(VII) 43989 [(5aS,9aS)-9a-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-methoxy-5a,6,7,9a-tetrahydrodibenzo[b,d]furan-1-yl]methyl tert-butyl(dimethyl)silyl ether; [[(5aS,9aS)-9a-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-methoxy-5a,6,7,9a-tetrahydrodibenzo[b,d]furan-1-yl]methoxy](tert-butyl)dimethylsilane C27H46O4Si2 详情 详情
(VIII) 43990 [(5aS,9aS)-9a-(hydroxymethyl)-4-methoxy-5a,6,7,9a-tetrahydrodibenzo[b,d]furan-1-yl]methanol C15H18O4 详情 详情
(IX) 43991 (5aS,9aS)-9a-(hydroxymethyl)-4-methoxy-5a,6,7,9a-tetrahydrodibenzo[b,d]furan-1-carbaldehyde C15H16O4 详情 详情
(X) 43992 [(4aS)-6-methoxy-9-[(methylamino)methyl]-4,4a-dihydrodibenzo[b,d]furan-9(3H)-yl]methanol C16H21NO3 详情 详情
(XI) 43993 tert-butyl [(5aS,9aS)-9a-(hydroxymethyl)-4-methoxy-5a,6,7,9a-tetrahydrodibenzo[b,d]furan-1-yl]methyl(methyl)carbamate C21H29NO5 详情 详情
(XII) 43994 tert-butyl [(5aS,9aR)-9a-formyl-4-methoxy-5a,6,7,9a-tetrahydrodibenzo[b,d]furan-1-yl]methyl(methyl)carbamate C21H27NO5 详情 详情
(XIII) 25649 (methoxymethyl)(triphenyl)phosphonium bromide C20H20BrOP 详情 详情
(XIV) 43995 tert-butyl [(5aS,9aR)-4-methoxy-9a-[(Z)-2-methoxyethenyl]-5a,6,7,9a-tetrahydrodibenzo[b,d]furan-1-yl]methyl(methyl)carbamate C23H31NO5 详情 详情
(XV) 43996 (4aS,8aR)-11-methyl-5,6,11,12-tetrahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-3-yl methyl ether; (4aS,8aR)-3-methoxy-11-methyl-5,6,11,12-tetrahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepine C17H19NO2 详情 详情
(XVI) 43997 (4aS,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepine; (4aS,8aS)-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-3-yl methyl ether C17H21NO2 详情 详情
(XVII) 43998 (1aS,3aR,4aS,4bR)-11-methoxy-7-methyl-2,3,3a,4a,5,6,7,8-octahydro-1aH-oxireno[2',3':4,5][1]benzofuro[3a,3,2-ef][2]benzazepine; (1aS,3aR,4aS,4bR)-7-methyl-2,3,3a,4a,5,6,7,8-octahydro-1aH-oxireno[2',3':4,5][1]benzofuro[3a,3,2-ef][2]benzazepin-11-yl methyl ether C17H21NO3 详情 详情
(XVIII) 43999 (4aS,7S,8S,8aR)-3-methoxy-11-methyl-7-(phenylselanyl)-5,6,7,8,9,10,11,12-octahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-8-ol C23H27NO3Se 详情 详情
(XIX) 44000 (4aS,8R,8aR)-3-methoxy-11-methyl-5,8,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-8-ol C17H21NO3 详情 详情
Extended Information