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【结 构 式】 
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【分子编号】63611 【品名】methyl 4-[(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate 【CA登记号】 |
【 分 子 式 】C31H38N2O4 【 分 子 量 】502.6538 【元素组成】C 74.08% H 7.62% N 5.57% O 12.73% |
合成路线1
该中间体在本合成路线中的序号：(X)In an alternative synthesis, which does not utilize the alkaloid catharanthine, Sharpless asymmetric epoxidation of 2-ethyl-2-propenol (I) in the presence of ( )-diethyl tartrate provides (R)-2-ethyl-2,3-epoxypropanol (II). Subsequent addition of allylmagnesium chloride (III) to epoxide (II) leads to diol (IV), which is further protected as the corresponding acetonide (V) with 2,2 dimethoxypropane and p-TsOH. Ozonolysis of the terminal olefin (V) gives rise to aldehyde (VI). Condensation of aldehyde (VI) with the indoloazapine (VII) furnishes the bridged azepine (VIII) as a diastereomeric mixture. Without isolation, this mixture of amines is N-alkylated with benzyl bromide, and the resultant ammonium salts (IX) are subjected to rearrangement in boiling MeOH in the presence of Et3N to provide an equimolecular mixture of the tetracyclic diastereoisomers (X) and (XI) (5).
| 【1】 Kuehne, M.E.; Matson, P.A..; Bornmann, W.G.; Enantioselective syntheses of vinblastine, leurosidine, vincovaline, and 20'-epi-vincovaline. J Org Chem 1991, 56, 2, 513. |
| 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) | 63603 | 2-ethyl-2-propen-1-ol | C5H10O | 详情 | 详情 | |
| (II) | 63604 | (2-ethyl-2-oxiranyl)methanol | C5H10O2 | 详情 | 详情 | |
| (III) | 61128 | C4H8 | 详情 | 详情 | ||
| (IV) | 63605 | 2-ethyl-5-hexene-1,2-diol | C8H16O2 | 详情 | 详情 | |
| (V) | 63606 | 4-(3-butenyl)-4-ethyl-2,2-dimethyl-1,3-dioxolane | C11H20O2 | 详情 | 详情 | |
| (VI) | 63607 | 3-(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)propanal | C10H18O3 | 详情 | 详情 | |
| (VII) | 63608 | methyl 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate | C14H16N2O2 | 详情 | 详情 | |
| (VIII) | 63609 | methyl 15-{2-[(4S)-4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl}-8,12-diazatetracyclo[10.2.1.0~1,9~.0~2,7~]pentadeca-2,4,6,9-tetraene-10-carboxylate | C24H32N2O4 | 详情 | 详情 | |
| (IX) | 63610 | 12-benzyl-15-{2-[(4S)-4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl}-10-(methoxycarbonyl)-8-aza-12-azoniatetracyclo[10.2.1.0~1,9~.0~2,7~]pentadeca-2,4,6,9-tetraene bromide | C31H39BrN2O4 | 详情 | 详情 | |
| (X) | 63611 | methyl 4-[(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O4 | 详情 | 详情 | |
| (XI) | 63612 | methyl 4-[(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)Acidic hydrolysis of the mixture of diastereoisomeric acetonides (X) and (XI) leads to the respective diols, which are then separated by flash chromatography. After selective tosylation of the primary hydroxyl group of isomer (XII) with p-toluenesulfonic anhydride, the remaining tertiary hydroxyl is protected by silylation with trimethylsilyl triflate to furnish (XIII). Chlorination of (XIII) with tert-butyl hypochlorite leads to (XIV), which is then coupled to vindoline (XV) in the presence of AgBF4 to afford the bis-indolyl derivative (XVI) (5).
| 【1】 Kuehne, M.E.; Matson, P.A..; Bornmann, W.G.; Enantioselective syntheses of vinblastine, leurosidine, vincovaline, and 20'-epi-vincovaline. J Org Chem 1991, 56, 2, 513. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 63611 | methyl 4-[(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O4 | 详情 | 详情 | |
| (XI) | 63612 | methyl 4-[(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O4 | 详情 | 详情 | |
| (XII) | 63613 | methyl 4-[2-hydroxy-2-(hydroxymethyl)butyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C28H34N2O4 | 详情 | 详情 | |
| (XIII) | 63614 | methyl 4-{2-({[(4-methylphenyl)sulfonyl]oxy}methyl)-2-[(trimethylsilyl)oxy]butyl}-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C38H48N2O6SSi | 详情 | 详情 | |
| (XIV) | 63615 | methyl 6-chloro-4-{2-({[(4-methylphenyl)sulfonyl]oxy}methyl)-2-[(trimethylsilyl)oxy]butyl}-3-(phenylmethyl)-2,3,3a,4,5,6-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C38H47ClN2O6SSi | 详情 | 详情 | |
| (XV) | 63596 | methyl 4-(acetyloxy)-3a-ethyl-5-hydroxy-6-methyl-8-(methyloxy)-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate | C25H32N2O6 | 详情 | 详情 | |
| (XVI) | 63616 | methyl 4-(acetyloxy)-3a-ethyl-5-hydroxy-6-methyl-8-(methyloxy)-9-[6-[(methyloxy)carbonyl]-4-{2-({[(4-methylphenyl)sulfonyl]oxy}methyl)-2-[(trimethylsilyl)oxy]butyl}-3-(phenylmethyl)-2,3,3a,4,5,6-hexahydro-1H-pyrrolo[2,3-d]carbazol-6-yl]-3a,4,5,5a,6, | C63H78N4O12SSi | 详情 | 详情 |