【结 构 式】 |
【药物名称】(+)-Deoxoartelinic acid 【化学名称】(+)-4-[2-[(3R,5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-Trimethylperhydro-3,12-epoxypyrano[4,3-j]-1,2-benzodioxepin-10-yl]ethyl]benzoic acid 【CA登记号】150894-00-1 (undefined stereoch.) 【 分 子 式 】C24H32O6 【 分 子 量 】416.51904 |
【开发单位】London School Hygiene Tropical Medicine (Originator), Northwick Park Inst. Medical Research (Originator), Yonsei University (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Antimalarials, Treatment of Protozoal Diseases |
合成路线1
The title compound is prepared starting from artemisinic acid (I), which is extracted from the leaves of Artemisia annua. Esterification of (I) with ethereal diazomethane affords methyl ester (II). Reduction of (II) by means of lithium or sodium borohydride and NiCl2 leads to the saturated ester (III), which is further reduced with DIBAL to the aldehyde (IV). Condensation of (IV) with the sulfur ylide generated from trimethylsulfonium iodide and KOH furnishes epoxide (V). Then, epoxide ring opening with the Grignard reagent (VI) gives alcohol (VII). Photooxigenative cyclization of (VII) produces the artemisinin derivative (VIII). Finally, oxidative vinyl group cleavage employing KMnO4 yields the target carboxylic acid. (1,2)
【1】 McChesney, J.D.; Jung, M.; Method of preparing (+)-deoxoartemisinin and selected analogues of (+)-deoxoartemisinin. US 5225562 . |
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) | 10222 | 2-[(1R,4R,4aS,8aR)-4,7-Dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]acrylic acid; Artemisinic acid | C15H22O2 | 详情 | 详情 | |
(II) | 64099 | methyl 2-[(1R,4R,4aS,8aR)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]acrylate | C16H24O2 | 详情 | 详情 | |
(III) | 10235 | methyl 2-[(1R,4R,4aS,8aS)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]propanoate | C16H26O2 | 详情 | 详情 | |
(IV) | 64101 | (2R)-2-[(1R,4R,4aS,8aS)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]propanal | C15H24O | 详情 | 详情 | |
(V) | 64102 | (2S)-2-{(1R)-1-[(1R,4R,4aS,8aS)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]ethyl}oxirane | C16H26O | 详情 | 详情 | |
(VI) | 64103 | chloro(4-vinylbenzyl)magnesium | C9H9ClMg | 详情 | 详情 | |
(VII) | 64104 | (3R,4R)-4-[(1R,4R,4aS,8aS)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]-1-(4-vinylphenyl)-3-pentanol | C25H36O | 详情 | 详情 | |
(VIII) | 64105 | 10-[2-(4-ethenylphenyl)ethyl]-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadecane | C25H34O4 | 详情 | 详情 |