一种用于方便的固体相合成N端酸胺的试剂,用于化学选择性结合
Takeo Fukuzumi1, Jeffrey W Bode
1Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA.
一种新型的N-硫基酸氨酸试剂有效地将N-终端胺转化为氧胺,保持立体化学. 这些基胺使得与α-酸具有化学选择性胺基键的形成.
科学领域:
- 有机化学 有机化学
- 类化学 类化学
- 合成方法论 合成方法论
背景情况:
- 基修饰对于药物发现和生物化学研究至关重要.
- 酸N-终端的选择性功能化带来了合成挑战.
- 现有的方法可能会遭受过度氧化或失去了立体化学完整性.
研究的目的:
- 开发一种新的试剂,用于选择性地将N端胺转化为氧胺.
- 为了使随后的化学选择性胺基键与α-酸形成.
- 为了确保在转化过程中保持立体化学.
主要方法:
- 合成一种新型N-硫基西里丁试剂.
- 试剂与N端胺的反应.
- 由此产生的N端氧胺的特征.
- 随后与α-酸一起形成胺键.
- 使用racemic和enantipure试剂对立体化学结果的调查.
主要成果:
- 这种N-硫基西里丁试剂成功地将N-终端氨基酸转化为氧胺.
- 反应没有过度氧化或立体化学侵蚀.
- 合成的N终端氧胺作为基质用于与α-酸的化学选择性反应.
- 试剂的对抗剂版本解决了立体化学不匹配,支持了拟议的机制.
结论:
- 一种新的N-sulfonyloxaziridine试剂为N-终端胺转化为氧胺提供了一种可靠的方法.
- 这种方法保留了立体化学,并使下游的化学选择性胺基键形成成为可能.
- 抗抗试剂的开发提高了这种转换的实用性和机制理解.
更多相关视频
08:55Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles (PPAs) and Related Biomaterials
Published on: June 25, 2018
12:02An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity
Published on: November 2, 2016
相关概念视频
Preparation of 1° Amines: Azide Synthesis
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Preparation of 1° Amines: Gabriel Synthesis
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Preparation of Amines: Reductive Amination of Aldehydes and Ketones
Preparation of Amides
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
Amines to Amides: Acylation of Amines
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Acid Halides to Amides: Aminolysis
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
