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通过化学选择性血清结合的循环化通过达普托米辛的总合成
Hiu Yung Lam1, Yinfeng Zhang, Han Liu
1Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, People's Republic of China.
Journal of the American Chemical Society
|April 9, 2013
概括
研究人员实现了新型抗生素达普托米的总合成. 这一突破使得达普托类型的制造成为可能,以探索新药开发的结构-活性关系.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 抗生素研究 抗生素研究
背景情况:
- 达普托米辛是一种重要的脂类抗生素,是几十年来首个推出的新类抗生素.
- 它的复杂的循环depsipeptide结构提出了相当大的合成挑战.
- 了解其结构-活性概况对于开发下一代抗生素至关重要.
研究的目的:
- 为了实现天然产品抗生素达普米辛的总合成.
- 为了建立一个合成框架来产生达普托米辛类似物.
- 为了促进达普托米辛的结构-活性关系研究.
主要方法:
- 采用了一个融合合成策略.
- 通过高效的血清酶结合,实现了宏环化.
- 一种新的方法涉及三氨酸化,臭氧化和金氨酸被用于化.
主要成果:
- 成功完成了达普托米辛的总合成.
- 开发了一种有效的循环脱类的宏循环化方法.
- 克服了涉及非蛋白质原性氨基酸的具有挑战性的化过程.
结论:
- 开发的合成途径为达普素模拟合成提供了一个强大的平台.
- 这项工作为详细的结构-活动关系研究奠定了基础.
- 这种合成为开发基于达普素的新型治疗方法开辟了道路.
相关概念视频
Olefin Metathesis Polymerization: Acyclic Diene Metathesis (ADMET)
Acyclic diene metathesis polymerization or ADMET polymerization involves cross-metathesis of terminal dienes, such as 1,8-nonadiene, to give linear unsaturated polymer and ethylene. As ADMET is a reversible process, the formed ethylene gas must be removed from the reaction mixture to complete the polymerization process.
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
Intramolecular Claisen Condensation of Dicarboxylic Esters: Dieckmann Cyclization
Dieckmann cyclization is an intramolecular Claisen condensation of diesters. The reaction occurs in the presence of a base and generates a cyclic β-ketoester as the final product. Commonly, 1, 6 and 1, 7-diesters are preferred substrates for the reaction since the generated five, and six-membered cyclic β-keto esters are particularly more stable.
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.

