Synthesis of an antitumor active chelerythrine type alkaloid using Claisen rearrangement of a propargyl ether

利用炔丙醚克莱森重排合成抗肿瘤活性白屈菜红碱型生物碱

• 批准号: 61570992
• 负责人: ISHII Hisashi
• 金额: $ 1.15万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570992/
• 关键词: synthesis; antitumor active alkaloid; Claisen rearrangement; furan ring cleavage; propargy ether; ケレリスリン合成; フラン環の開裂; プロパルギルエーテル; クライゼン転位; 合成; 抗腫瘍性塩基; ケレリスリン

1. Claisen Rearrangement of Aryl Propargyl Ether in the Presence of CsF: We found that Claisen rearrangement of the propargyl ether (1) in the presence of CsF , easily prepared, gave only the furan (3) but not the pyran (2) . This new reaction was examined in detail using the -naphthol derivative (4). The following facts were found on formation of a furan ring: (a) The best solvent was PHNET_2. (b) Other additives ex-cept CsF could not act. (c) A catalytic amount of CsF was enough, but practically about equimolar amount of it was needed. Heating 5__-, 6__- and the acetal of 7__- in PhNEt_2 containing CsF gave the corresponding furans in good yields, respectively, indicating generality of the reaction.KA2. Cleavage of the Furan Ring: The furan (8) derived from 7__- was used as a model compound for cleavage reaction of a furan ring. Successive treatment of 8__- with a stoichiometric amount of OsO_4, NaIO_4, and dil. NaHCO_3 aq. provided the desired salicylaldehyde (9) in satisfactory yield.3. Synthesis of Chelerythrine (11): The aldehyde (10) was prepared from 3__- using the method mentioned adove. Treatment of the methyl ether of 10__- with TsOH resulted in deprotection and cyc-lization to give chelerythrine (11). We succeeded in synthesizing a chelerythrine type alkaloid.KA

1.芳基炔丙基醚在CsF存在下的Claisen重排反应：我们发现炔丙基醚（1）在CsF存在下的Claisen重排反应只生成呋喃（3），而不生成吡喃（2）。用β-萘酚衍生物（4）详细研究了这一新反应.实验结果表明：（a）PHNET_2为最佳溶剂; (b)除CsF外，其它添加剂均不起作用。(c)催化量的CsF是足够的，但实际上需要大约等摩尔量的CsF。在含CsF的PhNEt_2中加热5__-、6__-和7__-的缩醛，分别以良好的产率得到相应的呋喃，表明该反应具有普遍性。呋喃环的断裂：将衍生自7__-的呋喃（8）用作呋喃环断裂反应的模型化合物。用化学计量的OsO_4、NaIO_4和dil. NaHCO_3水溶液以令人满意的产率提供所需的水杨醛（9）。白屈菜红碱（11）的合成：以3__-为原料，按上述方法合成了醛（10）.用TsOH处理10__-的甲醚，脱保护，环化得白屈菜红碱（11）。我们成功地合成了白屈菜红碱型生物碱KA