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【结 构 式】 
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【分子编号】35103 【品名】8-[3-[tert-butyl(dimethyl)silyl]-2-propynyl]-5-ethyl-5-hydroxy-7-iodo-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione 【CA登记号】 |
【 分 子 式 】C20H28INO4Si 【 分 子 量 】501.43663 【元素组成】C 47.91% H 5.63% I 25.31% N 2.79% O 12.76% Si 5.6% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The known enol ether (I) was dihydroxylated with OsO4 and then oxidatively cleaved to the keto formate (II) by means of Pb(OAc)4. Reformatskii reaction of (II) with (tert-butoxycarbonyl)methylzinc bromide gave hydroxyester (III). Further cyclization of (III) using trifluroacetic acid produced lactone (IV). Halogenation with iodine monochloride afforded iodopyridine (V). Then, cleavage of the methyl ether of (V) employing trimethylsilyl iodide generated the pyridone lactone (VI), which was N-alkylated with 3-(tert-butyldimethylsilyl)propargyl bromide (VII), yielding (VIII). Finally, radical annulation of (VIII) with phenyl isonitrile (IX) in the presence hexamethylditin furnished the title pentacyclic compound.
| 【1】 Bom, D.; et al.; Novel A,B,E-ring-modified camptothecins displaying high lipophilicity and markedly improved human blood stabilities. J Med Chem 1999, 42, 16, 3018. |
| 【2】 Burke, T.G.; Curran, D.P.; Bom, D. (University of Kentucky; University of Pittsburgh); Camptothecin analogs and methods of preparation thereof. WO 0061146 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 40586 | bromo[2-(tert-butoxy)-2-oxoethyl]zinc | C6H11BrO2Zn | 详情 | 详情 | ||
| (I) | 35096 | 4-ethyl-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridin-8-yl methyl ether; 4-ethyl-8-methoxy-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridine | C14H21NO2Si | 详情 | 详情 | |
| (II) | 35097 | [2-methoxy-4-propionyl-6-(trimethylsilyl)-3-pyridinyl]methyl formate | C14H21NO4Si | 详情 | 详情 | |
| (III) | 35098 | tert-butyl 3-[3-[(formyloxy)methyl]-2-methoxy-6-(trimethylsilyl)-4-pyridinyl]-3-hydroxypentanoate | C20H33NO6Si | 详情 | 详情 | |
| (IV) | 35099 | 5-ethyl-5-hydroxy-9-methoxy-7-(trimethylsilyl)-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one | C15H23NO4Si | 详情 | 详情 | |
| (V) | 35100 | 5-ethyl-5-hydroxy-7-iodo-9-methoxy-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one | C12H14INO4 | 详情 | 详情 | |
| (VI) | 35101 | 5-ethyl-5-hydroxy-7-iodo-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione | C11H12INO4 | 详情 | 详情 | |
| (VII) | 35102 | (3-bromo-1-propynyl)(tert-butyl)dimethylsilane | C9H17BrSi | 详情 | 详情 | |
| (VIII) | 35103 | 8-[3-[tert-butyl(dimethyl)silyl]-2-propynyl]-5-ethyl-5-hydroxy-7-iodo-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione | C20H28INO4Si | 详情 | 详情 | |
| (IX) | 35104 | Benzonitrile | 100-47-0 | C7H5N | 详情 | 详情 |