不对称的C型乙二烯酸的总合成: (+) - 塔拉西米丁和 (+) - 塔拉西胺
Quanzheng Zhang1, Zhao Yang1, Qi Wang1
1Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China.
Journal of the American Chemical Society
|May 3, 2021
概括
这项研究提供了第一个 (+) - 塔拉西米丁和 (+) - 塔拉萨胺,C20-diterpenoid类化合物的不对称的总合成. 关键步骤包括循环添加以构建奇拉核和 dearomative cyclopropanation 以形成B环并安装关键基.
科学领域:
- 有机化学
- 自然产品合成
- 医学化学
背景情况:
- 迪特类类化合物,特别是像塔拉西米丁和塔拉萨胺这样的类化合物,是具有潜在生物活性的复杂天然产物.
- 这种复杂分子的总合成在立体化学控制和环结构方面提出了重大挑战.
研究的目的:
- 实现 (+) - 塔拉西米丁和 (+) - 塔拉萨胺的第一个不对称的总合成.
- 开发新型合成策略,用于构建六环素骨架.
- 建立安装关键功能组的有效方法,例如赤道C7-OH.
主要方法:
- 亚甲酸的不对称的1,3-二极循环添加,以产生一种奇拉四环中间体.
- 一个环的dearomative循环化.
- 一个循环的核性环开口与水 (SN2类似的机制).
主要成果:
- 成功合成 (+) - 塔拉西米丁和 (+) - 塔拉萨胺.
- 在关键的循环添加步骤中具有高的区域选择性和扩散选择性,从一个中诱导出四个新的性中心.
- 通过循环和环开口,有效地构建B环并精确地安装赤道C7-OH组.
结论:
- 开发的合成途径提供了一个可靠的平台来获取 hetidine 类型的二类化物.
- 关键的转换表明了复杂分子组合和立体化学控制的强大策略.
- 这项工作扩大了天然产品化学的合成工具包,并可能促进这些类化合物的进一步生物评估.
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