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【结 构 式】 
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【分子编号】30843 【品名】(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-ol 【CA登记号】 |
【 分 子 式 】C34H36O6 【 分 子 量 】540.65624 【元素组成】C 75.53% H 6.71% O 17.76% |
合成路线1
该中间体在本合成路线中的序号：(IV)In the first reaction step phenyl phosphate dichloride (I) and 2-chloroethylamine hydrochloride are reacted in dichloromethane with triethylamine as base to give phenyl N,N'-di-(2-chloroethyl)phosphoric acid diamide (II). Hydrogenation of compound (II) with platinic oxide/hydrogen in methanol yields N,N'-di-(2-chloroethyl)phosphoric acid diamide (III), which directly crystallizes in the methanolic solution. 2,3,4,6-6-Tetra-O-benzyl-alpha-D-glucopyranose (IV) and trichloroacetonitrile react in ethyl acetate with sodium hydride as catalyst to yield O-(2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl) trichloroacetimidate (V). A mixture of the imidate (V) and compound (III) in ethyl acetate is warmed up to 60 C. After filtration and concentration, 2,3,4,6-tetra-O-benzyl-beta-D-glucopyranosyl N,N'-di-(2-chloroethyl)phosphoric acid diamide (VI) crystallizes. Finally, compound (VI) is hydrogenated with palladium catalyst in acetone/water (80:20) to give beta-D-glucopyranosyl N,N'-di-(2-chloroethyl)phosphoric acid diamide. The solution is filtered and concentrated. The residual water is lyophilisated and the lyophilisate is crystallized in acetone/water.
| 【1】 Niemeyer, U.; Peter, G.; Schuessler, M.; Voss, A.; Schupke, H.; Klenner, T.; Wiessler, M.; Engel, J.; Glufosfamide. Drugs Fut 2000, 25, 8, 791. |
| 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) | 39640 | Phenyl dichlorophosphate;phenyl phosphorodichloridate | 770-12-7 | C6H5Cl2O2P | 详情 | 详情 |
| (II) | 39641 | Phenyl N,N'-Bis(2-Chloroethyl)Phosphorodiamidate; 2-Chloroethyl-[(2-Chloroethylamino)-(Phenoxy)Phosphoryl]Amine; Nsc318225 | 70772-68-8 | C10H15Cl2N2O2P | 详情 | 详情 |
| (III) | 39642 | N,N'-bis(2-chloroethyl)phosphorodiamidic acid | C4H11Cl2N2O2P | 详情 | 详情 | |
| (IV) | 30843 | (2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-ol | C34H36O6 | 详情 | 详情 | |
| (V) | 39643 | (2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl 2,2,2-trichloroethanimidoate | C36H36Cl3NO6 | 详情 | 详情 | |
| (VI) | 39644 | C38H45Cl2N2O7P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Condensation of the magnesium iodide salt of 5-(benzyloxy)indole (I) with N-(benzyloxymethyl)-3,4-dibromomaleimide (II) provided the monoindolyl maleimide (III). Coupling of (III) with the benzyl-protected glucose (IV) via Mitsunobu reaction afforded the glycosylated indole (V). A second indolyl group was then introduced in (V) to give the bisindolylmaleimide (VI), which was oxidatively cyclized to the indolocarbazole (VII) using palladium bis(trifluoroacetate). Finally, hydrogenolysis of the benzyl protecting groups of (VII) over Pd/C furnished the title compound.
| 【1】 Lineswala, J.P.; Kuffel, M.J.; Zhang, H.; Aytes, S.A.; Zembower, D.E.; Ames, M.M.; Indolocarbazole poisons of human topoisomerase I: Regioisomeric analogues of ED-110. Bioorg Med Chem Lett 1999, 9, 2, 145. |
| 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) | 30840 | 5-Benzyloxyindole; benzyl 1H-indol-5-yl ether; 5-(benzyloxy)-1H-indole | 1215-59-4 | C15H13NO | 详情 | 详情 |
| (II) | 30841 | 1-[(benzyloxy)methyl]-3,4-dibromo-1H-pyrrole-2,5-dione | C12H9Br2NO3 | 详情 | 详情 | |
| (III) | 30842 | 3-[5-(benzyloxy)-1H-indol-3-yl]-1-[(benzyloxy)methyl]-4-bromo-1H-pyrrole-2,5-dione | C27H21BrN2O4 | 详情 | 详情 | |
| (IV) | 30843 | (2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-ol | C34H36O6 | 详情 | 详情 | |
| (V) | 30844 | 1-[(benzyloxy)methyl]-3-(5-(benzyloxy)-1-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-1H-indol-3-yl)-4-bromo-1H-pyrrole-2,5-dione | C61H55BrN2O9 | 详情 | 详情 | |
| (VI) | 30845 | 3-[5-(benzyloxy)-1H-indol-3-yl]-1-[(benzyloxy)methyl]-4-(5-(benzyloxy)-1-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-1H-indol-3-yl)-1H-pyrrole-2,5-dione | C76H67N3O10 | 详情 | 详情 | |
| (VII) | 30846 | 3,9-bis(benzyloxy)-6-[(benzyloxy)methyl]-12-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione | C76H65N3O10 | 详情 | 详情 |