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【结 构 式】 
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【药物名称】Plaunotol, CS-684, Kelnac 【化学名称】(2Z,6E)-2-[(3E)-4,8-Dimethyl-3,7-nonanediyl]-6-methyl-2,6-octadiene-1,8-diol 【CA登记号】64218-02-6 【 分 子 式 】C20H34O2 【 分 子 量 】306.49278 |
【开发单位】Sankyo (Originator) 【药理作用】Antiulcer Drugs, GASTROINTESTINAL DRUGS |
合成路线1
By a Wittig condensation of 5,9-dimethyl-4,8-decadien-1-yltriphenylphosphonium iodide (I) with 4-methyl-6-tetrahydropyranyloxy-4-hexenal (II) using butyllithium as condensing agent in THF, followed by reaction with paraformaldehyde and sec-butyl lithiurn in the same solvent.
| 【1】 Ogiso, A.; et al.; Isolation and structure of antipeptic ulcer diterpene from Thai medicinal plant. Chem Pharm Bull 1978, 26, 10, 3117-23. |
| 【2】 Mishima, H.; Ogiso, A.; Kobayashi, S. (Sankyo Co., Ltd.); Polyprenyl derivatives. DE 2652256; FR 2332009; GB 1533377; JP 52062213; US 4059641 . |
| 【3】 Castaner, J.; Serradell, M.N.; Blancafort, P.; Plaunotol. Drugs Fut 1983, 8, 11, 930. |
合成路线2
The condensation of homogeranyl iodide (III) with diethyl ethoxycarbony-methylphosphonate (IV) by means of NaH in diethoxyethane gives the phosphorane (V), which by a Wittig condensation with 4-methyl-6-acetoxy-4-hexenal (VI) by means of NaH yields 7-(ethoxycarbonyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraen-1-ol acetate (VII). Finally, this compound is reduced and hydrolyzed by treatment with LiAlH4.
| 【1】 Mishima, H.; Ogiso, A.; Kobayashi, S.; Polyprenyl derivatives. CH 629471; DE 2652256; FR 2332009; GB 1533377; JP 52062213; US 4059641 . |
| 【2】 Castaner, J.; Serradell, M.N.; Blancafort, P.; Plaunotol. Drugs Fut 1983, 8, 11, 930. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 31112 | (6E)-9-iodo-2,6-dimethyl-2,6-nonadiene | C11H19I | 详情 | 详情 | |
| (IV) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (V) | 31113 | ethyl (5E)-2-(diethoxyphosphoryl)-6,10-dimethyl-5,9-undecadienoate | C19H35O5P | 详情 | 详情 | |
| (VI) | 31114 | (E)-3-methyl-6-oxo-2-hexenyl acetate | C9H14O3 | 详情 | 详情 | |
| (VII) | 31115 | ethyl (5E)-2-[(Z,4E)-6-(acetoxy)-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienoate | C24H38O4 | 详情 | 详情 |
合成路线3
The condensation of genanyl bromide (VIII) with methyl 4,4-dimethoxyacetylacetate (IX) by means of sodium ethoxide in refluxing ethanol gives 1,1-dimethoxy-6,10-dimethyl-5,9-undecadiene-2-one (X), which is submitted to a Wittig condensation with (4-methyl-6-tetrahydropyranyloxy-4-hexenyl)triphenyl phosphonium iodide by means of n-butyllithium in hexane yielding 7-formyl-3,11,15-trimethyl-2,6,10,14-hexadecatetraen-1-ol (XII). Finally, this compound is reduced with NaBH4 in ethanol.
| 【1】 Mishima, H.; Ogiso, A.; Kobayashi, S. (Sankyo Co., Ltd.); Polyprenyl piperazines. DE 2717990; FR 2348907; FR 2422617; GB 1534111; JP 52131507; US 4151357 . |
| 【2】 Castaner, J.; Serradell, M.N.; Blancafort, P.; Plaunotol. Drugs Fut 1983, 8, 11, 930. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 31116 | (2E)-1-bromo-3,7-dimethyl-2,6-octadiene; trans-Geranyl bromide; Geranyl bromide | 6138-90-5 | C10H17Br | 详情 | 详情 |
| (IX) | 31117 | methyl 4,4-dimethoxy-3-oxobutanoate | C7H12O5 | 详情 | 详情 | |
| (X) | 31118 | (5E)-1,1-dimethoxy-6,10-dimethyl-5,9-undecadien-2-one | C15H26O3 | 详情 | 详情 | |
| (XI) | 31119 | [(E)-4-methyl-7-(tetrahydro-2H-pyran-2-yloxy)-4-heptenyl](triphenyl)phosphonium iodide | C31H38IO2P | 详情 | 详情 | |
| (XII) | 31120 | (5E)-2-[(Z,4E)-6-hydroxy-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienal | C20H32O2 | 详情 | 详情 |