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【结 构 式】 
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【药物名称】 【化学名称】(±)-(2R*,5Z,9S*,10S*,16R*)-9-Acetoxy-10,2,10-(epoxymetheno)-1-benz[c]azacyclododeca-5-ene-3,7-diyne-1-carboxylic acid 4-chlorophenyl ester,mixture with (2R*,5Z,9R*,10S*,16R*)-isomer (2:1) 【CA登记号】 【 分 子 式 】C25H16ClNO5 【 分 子 量 】445.86297 |
【开发单位】Sanwa (Originator) 【药理作用】ONCOLYTIC DRUGS |
合成路线1
Treatment of quinoline (I) with ethynylmagnesium bromide (II) in THF at low temperature, and then with 4-chlorophenyl chloroformate (III) gave carbamate (IV). Subsequent deprotection of tert-butyldimethylsilyl group with p-toluenesulfonic acid yielded allyl alcohol (V), and this was stereoselectively epoxidized with m-chloroperbenzoic acid to give epoxyalcohol (VI). Coupling of (VI) with vinyl chloride (VII) in the presence of Pd(0)-CuI catalyst provided the enediyne compound (VIII). This was oxidized with Dess-Martin periodinane reagent to the aldehyde (IX). Finally, CsF-promoted cyclization in the presence of acetic anhydride provided the title compound as a 2:1 mixture of diastereoisomers, which could not be separated.
| 【1】 Unno, R.; et al.; Structure-activity relationships of cyclic enediynes related to dynemicin A-I. Synthesis and antitumor activity of 9-acetoxy enediynes equipped with aryl carbamate moieties. Bioorg Med Chem 1997, 5, 5, 883. |
| 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) | 17777 | tert-butyl(dimethyl)silyl 4-quinolinylmethyl ether; 4-([[tert-butyl(dimethyl)silyl]oxy]methyl)quinoline | C16H23NOSi | 详情 | 详情 | |
| (II) | 17778 | ETHYNYLMAGNESIUM BROMIDE; bromo(ethynyl)magnesium | 4301-14-8 | C2HBrMg | 详情 | 详情 |
| (III) | 17779 | 1-chloro-4-[(chlorocarbonyl)oxy]benzene | 7693-45-0 | C7H4Cl2O2 | 详情 | 详情 |
| (IV) | 17780 | 4-chlorophenyl (2R)-4-([[tert-butyl(dimethyl)silyl]oxy]methyl)-2-ethynyl-1(2H)-quinolinecarboxylate | C25H28ClNO3Si | 详情 | 详情 | |
| (V) | 17781 | 4-chlorophenyl (2R)-2-ethynyl-4-(hydroxymethyl)-1(2H)-quinolinecarboxylate | C19H14ClNO3 | 详情 | 详情 | |
| (VI) | 17782 | 4-chlorophenyl (1aS,2S,7bS)-2-ethynyl-7b-(hydroxymethyl)-1a,7b-dihydrooxireno[2,3-c]quinoline-3(2H)-carboxylate | C19H14ClNO4 | 详情 | 详情 | |
| (VII) | 17783 | [(Z)-4-chloro-3-buten-1-ynyl](trimethyl)silane | C7H11ClSi | 详情 | 详情 | |
| (VIII) | 17784 | 4-chlorophenyl (1aS,2S,7bS)-7b-(hydroxymethyl)-2-[(Z)-6-(trimethylsilyl)-3-hexene-1,5-diynyl]-1a,7b-dihydrooxireno[2,3-c]quinoline-3(2H)-carboxylate | C26H24ClNO4Si | 详情 | 详情 | |
| (IX) | 17785 | 4-chlorophenyl (1aS,2S,7bR)-7b-formyl-2-[(Z)-6-(trimethylsilyl)-3-hexene-1,5-diynyl]-1a,7b-dihydrooxireno[2,3-c]quinoline-3(2H)-carboxylate | C26H22ClNO4Si | 详情 | 详情 |