(+) -安菲迪诺化物A.的总合成 结构的阐明和合成的完成
Barry M Trost1, Paul E Harrington, John D Chisholm
1Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Journal of the American Chemical Society
|September 30, 2005
概括
细胞毒性宏化物 (+) - 氨基化物A的总合成是使用催化合实现的. 这种方法通过合成二聚体的NMR分析证实了天然产品的正确立体化学.
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
- 化学生物学 化学生物学
背景情况:
- (+) - 安菲迪诺利德A是一种具有复杂的20个成员环状结构的细胞毒性宏化物.
- 阐明这些天然产品的精确立体化学对于理解它们的生物活性和合成努力至关重要.
研究的目的:
- 为了实现 (+) - 安菲迪诺化A的总合成,A.
- 为了确认自然产品的拟议结构和相对立体化学.
- 为复杂的宏化物开发高效的合成策略.
主要方法:
- 用鲁丁催化基-基合被用来形成C15-C16键,构建了20个成员的巨型环.
- 从一个拟议的结构开始,合成安菲迪诺化物A的各种二聚体.
- 核磁共振 (NMR) 化学转移分析,将合成异构体与天然产品进行比较.
主要成果:
- 成功完成了 (+) - 氨基胺甲基的总合成.
- 通过分析NMR化学转移中的偏差,识别最初报告的立体化学中的结构错误.
- 合成化合物的光谱数据显示与天然材料有很好的一致性,证实了修订后的结构.
结论:
- 通过总合成和NMR分析, (+) - 氨基胺甲的结构和相对立体化学已经得到了最终确定.
- 合成途径提供了一种可靠的方法来获取安菲迪诺利德A及其类似物.
- 这项工作验证了NMR化学转移分析在结构阐明和复杂自然产品的立体化学赋值中的实用性.
相关概念视频
02:34Structural Isomerism
Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can be...
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can be...
01:15Carboxylic Acid Derivatives: Overview
Carboxylic acid derivatives are formed by replacing the hydroxyl group of carboxylic acids with a different functional group. The most common carboxylic acid derivatives are:
01:28Structures of Carboxylic Acid Derivatives
Structure of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...
01:19Structure of Amines
The hybridized nitrogen atom in amines possesses a lone pair of electrons and is bound to three substituents with a bond angle of around 108°, which is less than the tetrahedral angle of 109.5°. However, the C–N–H bond angle is slightly larger at 112°, with a carbon–nitrogen bond length of 147 pm. This carbon–nitrogen bond length of of amines is longer than the carbon–oxygen bond of alcohols (143 pm) but shorter than alkanes’ carbon–carbon bond (154 pm). These aspects are illustrated in Figure...
01:10Nomenclature of Aryl and Heterocyclic Amines
The simplest aromatic amine is phenylamine, which contains an –NH2 functionality directly attached to an aromatic ring. The name aniline is designated for this skeleton. As shown in Figure 1, the common names of the functionalized anilines involve prefixes ortho-, meta-, and para- to indicate the substitution position. Different functionalized aniline derivatives also have notable trivial names.
01:23Complexation Equilibria: Overview
Complexation reactions take place when dative or coordinate covalent bonds form between metal ions and ligands. The compounds formed in these reactions are called coordination compounds. The number of bonds formed between the metal ion and the ligands is called its coordination number. Generally, most metal ions in an aqueous solution are solvated by water molecules and thus exist as aqua complexes.
The equilibrium constant of the complexation reaction is represented as the formation constant...
The equilibrium constant of the complexation reaction is represented as the formation constant...