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【结 构 式】 
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【分子编号】40606 【品名】(3aS,8aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl methylcarbamate 【CA登记号】57-47-6 |
【 分 子 式 】C15H21N3O2 【 分 子 量 】275.35076 【元素组成】C 65.43% H 7.69% N 15.26% O 11.62% |
合成路线1
该中间体在本合成路线中的序号：(I)Hydrolysis of physostigmine (I) with either NaOMe in ethanol or NaOBu in refluxing butanol (better yield) gives eseroline (II), which is condensed with phenyl isocyanate (III) by means of NaOMe in benzene, Na in benzene or Na in ether/benzene.
| 【1】 Castañer, J.; Sorbera, L.A.; Phenserine Tartrate. Drugs Fut 2003, 28, 1, 18. |
| 【2】 Polonovski, M.; Study on the alkaloids of the Calabar bean (V). Action of phenyl isocyanate: Phenylic homologs of eserine and genserine. Bull Soc Chim Fr Mem 1916, 19, 46. |
| 【3】 Maggi, A.; Brufani, M.; Lappa, S.; Filocamo, L.; New acetylcholinesterease inhibitors. Drugs Fut 1997, 22, 4, 397. |
| 【4】 Yu, Q.-S.; Schonenberger, B.; Brossi, A.; Reactions of (-)-physostigmine and (-)-N-methylphysostigmine in refluxing butanol and at high temperature: Facile preparation of (-)-eseroline. Heterocycles 1987, 26, Suppl. 3, 1271-5. |
| 【5】 Castellano, C.; Pomponi, M.; Brufani, M.; Pagella, P.G.; Oliverio, A.; Marta, M.; Pavone, F.; New analogs of physostigmine: Alternative drugs for Alzheimer's disease?. Life Sci 1988, 43, 23, 1921. |
| 【6】 Greig, N.H.; et al.; Phenserine and ring C hetero-analogs: Drug candidates for the treatment of Alzheimer's disease. Med Res Rev 1995, 15, 1, 3. |
| 【7】 Brzostowska, M.; et al.; Phenylcarbamates of (-)-eseroline, (-)-N1-noreseroline and (-)-physovenol: Selective inhibitors of acetyl and,or butyrylcholinesterase. Med Chem Res 1992, 2, 4, 238. |
| 【8】 Pomponi, M.; Brufani, M.; Marta, M.; Pavone, F.; Oliverio, A.; Castellano, C. (Consiglio Nazionale delle Ricerche); Physostigmine derivs. with acetylcholinesterase inhibition properties, and the relative production process. EP 0154864; EP 0354594 . |
| 【9】 Brossi, A.; Brzostowska, M.; Rapoport, S.I.; Greig, N.; He, X.-S. (US Department of Health & Human Services); Substd. phenserines as specific inhibitors of acetylcholinesterase. EP 0606366; JP 1995503703; US 5171750; WO 9306105 . |
| 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) | 40606 | (3aS,8aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl methylcarbamate | 57-47-6 | C15H21N3O2 | 详情 | 详情 |
| (II) | 20365 | (3aS,8aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol | C13H18N2O | 详情 | 详情 | |
| (III) | 11289 | 1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate | 103-71-9 | C7H5NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The oxidation of eserine (I) by means of H2O2 and KHCO3 produced the geneseroline carbamate (II), which was hydrolyzed to geneseroline (III) employing 62% sulfuric acid at 85 C. The desired carbamate was then obtained by condensation of (III) with 2-ethylphenyl isocyanate (IV) either in the presence of K2CO3 in acetone or in the presence of t-BuOK under sonication, and the title compound was then isolated as the corresponding hydrochloride salt.
| 【1】 Ventura, P.; Pighi, R.; Servadio, V.; Pietra, C.; Amari, G.; Salsi, B.; Pivetti, F.; Delcanale, M.; Chiesi, P.; Villetti, G. (Chiesi Farmaceutici SpA); A process for the preparation of aminocarbonyl derivs. of geneseroline having selective brain anticholinesterase activity. WO 9919329 . |
| 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) | 40606 | (3aS,8aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl methylcarbamate | 57-47-6 | C15H21N3O2 | 详情 | 详情 |
| (II) | 40607 | (4aS,9aS)-2,4a,9-trimethyl-2,3,4,4a,9,9a-hexahydro[1,2]oxazino[6,5-b]indol-6-yl methylcarbamate | C15H21N3O3 | 详情 | 详情 | |
| (III) | 40608 | (4aS,9aS)-2,4a,9-trimethyl-2,3,4,4a,9,9a-hexahydro[1,2]oxazino[6,5-b]indol-6-ol | C13H18N2O2 | 详情 | 详情 | |
| (IV) | 40609 | 2-ethylphenyl isocyanate; 1-ethyl-2-isocyanatobenzene | 40411-25-4 | C9H9NO | 详情 | 详情 |