(-) - 纳卡多马林A的总合成
Pavol Jakubec1, Dane M Cockfield, Darren J Dixon
1Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Journal of the American Chemical Society
|November 4, 2009
概括
通过使用新的催化反应和高效的反应级联,实现了复杂的自然产物 (-) - - 纳卡多马林A的简洁合成. 这种立体选择性路径只需12个步骤就能提供大量的向分子.
科学领域:
- 有机化学 有机化学
- 自然产品的合成自然产品的合成
- 催化剂是一种催化剂.
背景情况:
- (-) 纳卡多马林A是一种具有建筑复杂性的海洋天然产品,具有潜在的生物学意义.
- 以前的合成可能是漫长的或缺乏高立体选择性.
研究的目的:
- 开发一种简短,高度刻板选择性和高效的合成路径,以获得 (-) - 纳卡多玛林A.
- 为复杂分子构造引入新的化学转换.
主要方法:
- 使用催化剂控制的键形成和单多步程序.
- 采用了强大的路径缩短反应级联,包括Z选择性宏环环闭合转化和散列选择性分子内循环.
- 集成的双功能器官催化剂用于迈克尔添加和尼特罗-曼尼克/乳酸化级联.
主要成果:
- 从商业上可用的材料中实现了 (-) - 纳卡多马林A的12步合成.
- 开发了前所未有的,高度刻板选择性的反应:Z-选择性的分子内朱莉亚-科西恩斯基反应,二分体选择性的分子内/循环反应,以及硫酸控制的Z-选择性的宏环环闭合转化.
- 在大量生产目标天然产品.
结论:
- 开发的合成策略是高度高效和立体选择性的.
- 新的化学转换是构建复杂分子架构的宝贵工具.
- 这种合成提供了一个可扩展的路径,以 (-) - 纳卡多玛林A.
相关概念视频
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.
2° Amines to N-Nitrosamines: Reaction with NaNO2
Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.

