通过四组件合和四环化步骤,在四个步骤中合成 (+) - α-诺林的总合成
Yuan Mi1, Jürg V Schreiber, E J Corey
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Journal of the American Chemical Society
|September 19, 2002
概括
一个新的四步合成 (+) - α-onocerin提供了一个高效的途径,这个复杂的四环三烯. 这种方法利用了新的策略来快速形成环和立体化学控制.
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
- 立体选择性合成 立体选择性合成
背景情况:
- 三聚是一种具有复杂结构的多种类型的自然产品.
- (+) -alpha-Onocerin是一种具有独特分子结构的C2-对称四环三烯.
- 复杂的自然产品的高效和enantioselective合成仍然是有机化学的一个重大挑战.
研究的目的:
- 开发 (+) - α-onocerin的一个简洁和enantioselective合成.
- 建立适用于复杂分子构造的新合成方法.
- 为了探索 (+) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 的二聚体的合成.
主要方法:
- 设计了一个四步合成序列.
- 关键步骤包括四个碎片的单组合,以形成一种性双环氧化物.
- 对于快速的碳循环环的形成,采用了阴离子-烯四环化.
- 采用了用于将乙烯基 tert-butyldimethylsilyl 以太转化为乙烯基三酸盐的新方法.
主要成果:
- 合成 (+) - 阿尔法 - 奥诺塞林是在四个步骤中实现的,总产量为31%.
- 合成证明了高的反抗选择性.
- 通过使用开发的方法,还合成了 (+) - α-onocerin 的二聚体.
- 新的乙烯基乙烯转化为乙烯基三叶酸的转化方法保留了烯的几何形状.
结论:
- 已经确立了 (+) - α-onocerin的显著短时间和高效的酶选择性合成.
- 开发的方法,包括阴离子-烯四环化和乙烯基三酸盐的形成,是广泛适用的.
- 这项工作为结构独特的四环三烯提供了有价值的合成途径.
相关概念视频
Conjugate Addition to α,β-Unsaturated Carbonyl Compounds
α,β-Unsaturated carbonyl compounds are molecules bearing a carbonyl and alkene functionality in conjugation with each other. The conjugation in the molecule leads to three resonance structures. The hybrid form exhibits two probable electrophilic sites: the carbonyl carbon and the β carbon.
Radical Formation: Overview
A bond can be broken either by heterolytic bond cleavage to form ions or homolytic bond cleavage to yield radicals. A fishhook arrow is used to represent the motion of a single electron in homolytic bond cleavage. There are two main sources from which radicals can be formed:
Radicals from spin-paired molecules:
Radicals can be obtained from spin-paired molecules either by homolysis or electron transfer. While two radicals are formed in the former, an electron is added in the latter, also known...
Radicals from spin-paired molecules:
Radicals can be obtained from spin-paired molecules either by homolysis or electron transfer. While two radicals are formed in the former, an electron is added in the latter, also known...
C–C Bond Formation: Aldol Condensation Overview
Aldol condensation is an important route in synthetic organic chemistry used to generate a new carbon–carbon bond under basic or acidic conditions. The aldol condensation reaction presented in Figure 1 constitutes an aldol addition reaction followed by the dehydration process.
Aldol Condensation with β-Diesters: Knoevenagel Condensation
The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as β-diesters to produce substituted olefins.
Aldol Condensation vs Claisen Condensation
Aldol condensation is an acid or base-catalyzed condensation between aldehydes or ketones to give an α,ꞵ-unsaturated carbonyl compound. A base-promoted condensation between ester molecules to produce a ꞵ-ketoester is known as the Claisen condensation. In the presence of a base, both reactions involve deprotonation of the acidic α hydrogen to produce the corresponding enolates. The nucleophilic enolates attack their respective nonenolized carbonyl compound forming a tetrahedral intermediate.
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, β-ketoesters, or β-diketones) and α,β-unsaturated carbonyl acceptors. Named after Sir Robert Robinson, who discovered it, this reaction yields a six-membered ring with three new C–C bonds (two σ bonds and one π bond).

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