关于 (±) - 比萨博斯奎尔A的总合成
Christopher W am Ende1, Zhou Zhou, Kathlyn A Parker
1Department of Chemistry, Stony Brook University, Stony Brook, New York 11794, USA.
Journal of the American Chemical Society
|December 28, 2012
概括
研究人员使用14步路线合成了bisabosqual A,一种新的烯合成酶抑制剂. 关键的并联激素循环有效地构建了具有高立体控制的复杂四环核心.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 合成化学 合成化学
背景情况:
- 烯合成酶是胆固醇生物合成中的一个关键酶.
- 斯卡伦合成酶的抑制剂是高胆固醇血症的潜在治疗剂.
- 比萨博斯奎尔A是一种具有复杂四环结构的新型抑制剂.
研究的目的:
- 开发一种新型烯合成酶抑制剂,bisabosqual A. A. 的合成途径.
- 建立一个高效和立体选择性合成的四环核心结构.
主要方法:
- 从商业上可用的原材料进行14步合成.
- 一个双重融合的合成策略.
- 一个关键的5 - exo,6 - exo基循环,以构建四环核.
- 区域选择性脱氧和立体选择性有机金属添加反应.
主要成果:
- 成功合成了比萨博斯奎尔A的合成.
- 完全功能化的四环芯的高效组装.
- 引入三个具有高度控制的立体中心.
- 展示区域选择性和立体选择性转换.
结论:
- 已经建立了一个可行的合成途径来获得bisabosqual A.
- 关键的根循环是构建复杂的多循环系统的有效方法.
- 综合强调了功能组操纵和立体中心引入的高效方法.
相关概念视频
02:23SN2 Reaction: Stereochemistry
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
01:22Electrophilic Aromatic Substitution: Sulfonation of Benzene
Sulfonation of benzene is a reaction wherein benzene is treated with fuming sulfuric acid at room temperature to produce benzenesulfonic acid. Fuming sulfuric acid is a mixture of sulfur trioxide and concentrated sulfuric acid.
01:30Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)
Nucleophilic substitution in aromatic compounds is feasible in substrates bearing strong electron-withdrawing substituents positioned ortho or para to the leaving group. The reaction proceeds via two steps: the addition of the nucleophile and the elimination of the leaving group.
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between the...
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between the...
01:14Alkylation 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.
01:11Nucleophilic Aromatic Substitution: Elimination–Addition
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is confirmed through isotopic...
01:07Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated β-keto acid.