氧化的welwitindolinones和 (-) -N-甲基welwitindolinone C isonitrile 的总合成
Kyle W Quasdorf1, Alexander D Huters, Michael W Lodewyk
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
Journal of the American Chemical Society
|January 13, 2012
概括
研究人员实现了复杂的天然产品 (-) -N-甲基welwitindolinone C isonitrile 和 3-基化welwitindolinones 的总合成. 的动态同位素效应增强了关键的烯插入反应,提高了合成效率.
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
- 药用化学 医学化学
背景情况:
- 韦尔维因多林是一种难以捉摸的海洋天然产品,具有潜在的生物活性.
- 以前的合成努力是有限的,突出了需要高效路线的需要.
研究的目的:
- 报告第一个 (-) -N-甲基双双 C isonitrile 的总合成.
- 为了开发合成路径为3-基化welwitindolinones.
- 在天然产品合成中研究动态同位素效应的有用性.
主要方法:
- 总合成利用战略性的动同位素效应.
- 晚期烯插入反应的优化.
- 立体化学的计算预测.
- 实验证实立体化学配置的实验证实.
主要成果:
- 成功完成了 (-) -N-甲基双双英多林C异.的总合成.
- 实现了3-基化welwitindolinones的有效合成.
- 的动态同位素效应显著提高了烯插入效率.
- 计算和实验研究证实了C3的立体化学.
结论:
- 开发的合成策略提供了重要的天然产品.
- 动态同位素效应的使用为优化具有挑战性的合成步骤提供了强大的工具.
- 这项工作推进了天然产品合成领域,并为进一步的生物评估提供了化合物.
相关概念视频
01:14Aldehydes and Ketones to Alkenes: Wittig Reaction Mechanism
The Wittig reaction, which converts aldehydes or ketones to alkenes using phosphorus ylides, proceeds through a nucleophilic addition‒elimination process.
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
01:19Aldehydes and Ketones to Alkenes: Wittig Reaction Overview
The Wittig reaction is the conversion of carbonyl compounds-aldehydes and ketones-to alkenes using phosphorus ylides, or the Wittig reagent. The reaction was pioneered by Prof. Georg Wittig, for which he was awarded the Nobel Prize in Chemistry.
01:19Nitrosation of Enols
The nitrosation reaction is one of the methods of preparing 1,2-diketones. The enol tautomer of the starting ketone reacts with sodium nitrite in hydrochloric acid, generating the 1,2-diketone after hydrolysis.
01:32Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction mixture.
03:00Preparation of Epoxides
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
01:12Preparation of Nitriles
One of the common methods to prepare nitriles is the dehydration of amides. This method requires strong dehydrating agents like phosphorous pentoxide or boiling acetic anhydride for converting amides to nitriles. Another reagent namely, thionyl chloride also accomplishes the dehydration of amides, where amide acts as a nucleophile. The first step of the mechanism involves the nucleophilic attack by the amide on the thionyl chloride to form an intermediate. In the next step, the electron pairs...