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【结 构 式】 
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【分子编号】26858 【品名】2-[5-(bis(acetoxy)[bis[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]]-lambda(5)-bismuthanyl)-1H-indol-1-yl]ethyl tert-butyl(dimethyl)silyl ether 【CA登记号】 |
【 分 子 式 】C52H78BiN3O7Si3 【 分 子 量 】1150.44421 【元素组成】C 54.29% H 6.83% Bi 18.17% N 3.65% O 9.74% Si 7.32% |
合成路线1
该中间体在本合成路线中的序号：(Xa)Protection of 2-bromoethanol (I) upon treatment with 2-methoxypropene (II) gave a mixture of ketals (III) and (IV). This mixture was used for N-alkylation of 5-bromoindole (V) in the presence of KOH to afford, after ketal hydrolysis, 1-(2-hydroxyethyl)-5-bromoindole (VI) (1). Alternatively, compound (VI) was obtained by alkylation of 5-bromoindole (V) with ethylene oxide (VII) in the presence of NaOH in DMSO (2). The hydroxyl group of (VI) was then protected as the silyl ether (VII) by treatment with tert-butyldimethylsilyl chloride. Subsequent lithium-halogen exchange in (VIII) with tert-butyllithium, followed by reaction with bismuth trichloride provided the triindolyl bismuthane (IX) (1, 2). This was oxidized with either benzoyl peroxide (1) or peracetic acid (2) to produce the corresponding di(acyloxy) pentavalent bismuthanes (X).
| 【1】 Brands, K.M.J.; et al.; Mild aryl ether formation in the semisynthesis of the novel macrolide immunosuppressant L-732,531. J Org Chem 1998, 63, 19, 6721. |
| 【2】 Sinclair, P.J.; Goulet, M.; Wong, F.; Parsons, W.H.; Goulet, J.; Wyvratt, M.J. (Merck & Co., Inc.); O-Heteroaryl, O-alkylheteroaryl, O-alkenylheteroaryl and O-alkynylheteroaryl macrolides. EP 0532088; JP 1994116274; US 5252732; WO 9305058 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Xa) | 26858 | 2-[5-(bis(acetoxy)[bis[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]]-lambda(5)-bismuthanyl)-1H-indol-1-yl]ethyl tert-butyl(dimethyl)silyl ether | C52H78BiN3O7Si3 | 详情 | 详情 | |
| (Xb) | 26859 | 2-[5-(bis(benzoyloxy)[bis[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]]-lambda(5)-bismuthanyl)-1H-indol-1-yl]ethyl tert-butyl(dimethyl)silyl ether | C62H82BiN3O7Si3 | 详情 | 详情 | |
| (I) | 10059 | Ethylene bromohydrin; 2-Bromo-1-ethanol | 540-51-2 | C2H5BrO | 详情 | 详情 |
| (II) | 17354 | isopropenyl methyl ether; 2-methoxy-1-propene | 116-11-0 | C4H8O | 详情 | 详情 |
| (III) | 26853 | 2-(2-bromoethoxy)-2-methoxypropane | C6H13BrO2 | 详情 | 详情 | |
| (IV) | 26854 | 1-(2-bromoethoxy)-1-methylethyl 2-bromoethyl ether | C7H14Br2O2 | 详情 | 详情 | |
| (V) | 13309 | 5-Bromo-1H-indole; 5-Bromoindole | 10075-50-0 | C8H6BrN | 详情 | 详情 |
| (VI) | 26855 | 2-(5-bromo-1H-indol-1-yl)-1-ethanol | C10H10BrNO | 详情 | 详情 | |
| (VII) | 10393 | Oxirane; Ethylene oxide | 75-21-8 | C2H4O | 详情 | 详情 |
| (VIII) | 26856 | 2-(5-bromo-1H-indol-1-yl)ethyl tert-butyl(dimethyl)silyl ether | C16H24BrNOSi | 详情 | 详情 | |
| (IX) | 26857 | 2-(5-[bis[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]bismuthino]-1H-indol-1-yl)ethyl tert-butyl(dimethyl)silyl ether | C48H72BiN3O3Si3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(Xa)Arylation of ascomycin (XI) with the pentavalent bismuthanes (X) under catalysis of cupric acetate produced a mixture of the required indolyl ether (XII) and minor amounts of bis(indolyl) ether (XIII). Finally, after desilylation of (XII) and (XIII) by acid treatment in MeOH, the title monoindolyl ether was isolated by column chromatography.
| 【1】 Brands, K.M.J.; et al.; Mild aryl ether formation in the semisynthesis of the novel macrolide immunosuppressant L-732,531. J Org Chem 1998, 63, 19, 6721. |
| 【2】 Sinclair, P.J.; Goulet, M.; Wong, F.; Parsons, W.H.; Goulet, J.; Wyvratt, M.J. (Merck & Co., Inc.); O-Heteroaryl, O-alkylheteroaryl, O-alkenylheteroaryl and O-alkynylheteroaryl macrolides. EP 0532088; JP 1994116274; US 5252732; WO 9305058 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Xa) | 26858 | 2-[5-(bis(acetoxy)[bis[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]]-lambda(5)-bismuthanyl)-1H-indol-1-yl]ethyl tert-butyl(dimethyl)silyl ether | C52H78BiN3O7Si3 | 详情 | 详情 | |
| (Xb) | 26859 | 2-[5-(bis(benzoyloxy)[bis[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]]-lambda(5)-bismuthanyl)-1H-indol-1-yl]ethyl tert-butyl(dimethyl)silyl ether | C62H82BiN3O7Si3 | 详情 | 详情 | |
| (XI) | 14591 | 2-Amino-1,3,4-thiadiazole; 1,3,4-Thiadiazol-2-amine; 1,3,4-Thiadiazol-2-ylamine | 4005-51-0 | C2H3N3S | 详情 | 详情 |
| (XII) | 26860 | (1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-12-[(E)-2-((1R,3R,4R)-4-[[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone | C59H92N2O13Si | 详情 | 详情 | |
| (XIII) | 26861 | (1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-14-[[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]oxy]-12-[(E)-2-((1R,3R,4R)-4-[[1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1H-indol-5-yl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone | C75H115N3O14Si2 | 详情 | 详情 |