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【结 构 式】 
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【分子编号】48489 【品名】methyl (3aS,4R,11bR)-3-benzyl-4-[(2S)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate 【CA登记号】 |
【 分 子 式 】C31H38N2O5 【 分 子 量 】518.6532 【元素组成】C 71.79% H 7.38% N 5.4% O 15.42% |
合成路线1
该中间体在本合成路线中的序号：(XIIIb)In an alternative procedure, aldehyde (II) was condensed with the indoloazepine (VIII) bearing a chiral N-alpha-ferrocenylethyl substituent to provide an equimolecular mixture of two separable C-20 epimeric diastereomers (IX) and (X), each accompanied by a minor diastereoisomeric byproduct. Cleavage of the ferrocenyl substituent with HOAc at 70 C provided the secondary amines (XI) and (XII). In this cleavage, the C-3,C-7 epimeric products were formed in 12% yield and were separated by chromatography. The major secondary amines (XI) and (XII) were N-benzylated to provide the corresponding tertiary amines (XIII). Reductive ring cleavage, followed by hydrogenolysis of the N-benzyl group, then gave the tricyclic compounds (VI), which were cyclized and rearranged as above.
| 【1】 Kuehne, M.E.; et al.; Enantioselective syntheses of coronaridine and 18-methoxycoronaridine. Tetrahedron 2001, 57, 11, 2085. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIa) | 48480 | methyl (5R,7S)-5-[(2R)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-1,2,3,4,5,6,7,8-octahydroazonino[5,4-b]indole-7-carboxylate | C24H34N2O5 | 详情 | 详情 | |
| (VIb) | 48481 | methyl (5R,7S)-5-[(2S)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-1,2,3,4,5,6,7,8-octahydroazonino[5,4-b]indole-7-carboxylate | C24H34N2O5 | 详情 | 详情 | |
| (XIIIa) | 48488 | methyl (3aS,4R,11bR)-3-benzyl-4-[(2R)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O5 | 详情 | 详情 | |
| (XIIIb) | 48489 | methyl (3aS,4R,11bR)-3-benzyl-4-[(2S)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O5 | 详情 | 详情 | |
| (II) | 48474 | 4-(1,3-dioxolan-2-yl)-6-methoxyhexanal | C10H18O4 | 详情 | 详情 | |
| (VIII) | 48483 | C38H39FeN2O2P | 详情 | 详情 | ||
| (IX) | 48484 | C48H55FeN2O5P | 详情 | 详情 | ||
| (X) | 48485 | C48H55FeN2O5P | 详情 | 详情 | ||
| (XI) | 48486 | methyl (3aS,4R,11bR)-4-[(2R)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C24H32N2O5 | 详情 | 详情 | |
| (XII) | 48487 | methyl (3aS,4R,11bR)-4-[(2S)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C24H32N2O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIIIb)In an improved synthesis, condensation of the beta-dimethyltetramethylene-ferrocene derivative (XIV) with aldehyde (II) produced the unseparable C-20 epimeric mixture (XV) without appreciable amounts of diastereomeric byproducts. Cleavage of the chiral auxiliary group with HOAc under milder conditions furnished the secondary amines (XVI) with minimal C-3,C-7 epimerization. Benzylation of amines (XVI) then gave the enantiomerically pure tertiary amines (XIII), which were finally processed as above.
| 【1】 Kuehne, M.E.; et al.; Enantioselective syntheses of coronaridine and 18-methoxycoronaridine. Tetrahedron 2001, 57, 11, 2085. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIa) | 48486 | methyl (3aS,4R,11bR)-4-[(2R)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C24H32N2O5 | 详情 | 详情 | |
| (XVIb) | 48487 | methyl (3aS,4R,11bR)-4-[(2S)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C24H32N2O5 | 详情 | 详情 | |
| (XIIIa) | 48488 | methyl (3aS,4R,11bR)-3-benzyl-4-[(2R)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O5 | 详情 | 详情 | |
| (XIIIb) | 48489 | methyl (3aS,4R,11bR)-3-benzyl-4-[(2S)-2-(1,3-dioxolan-2-yl)-4-methoxybutyl]-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O5 | 详情 | 详情 | |
| (XVa) | 48491 | C40H52FeN2O5 | 详情 | 详情 | ||
| (XVb) | 48492 | C40H52FeN2O5 | 详情 | 详情 | ||
| (II) | 48474 | 4-(1,3-dioxolan-2-yl)-6-methoxyhexanal | C10H18O4 | 详情 | 详情 | |
| (XIV) | 48490 | C30H36FeN2O2 | 详情 | 详情 |