相关实验视频
Updated: Jun 23, 2025

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
通过耐表化直接氨解产生受约束的L-循环四甲
Huan Chen1, Yuchen Zhang2, Yuming Wen1
1Department of Chemistry, State University of New York, University at Albany, Albany, NY, 12222, USA.
合成受约束的循环是一种挑战. 一个新的β-thiolactone框架使直接氨解成为有效的,非epimerizable合成循环四甲,包括强大的微型阿片类受体激活剂.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 类化学 类化学
背景情况:
- 由于循环化约束,受约束的12个成员环合成是困难的.
- 过度激活会导致表皮化;不足激活会导致寡合化.
研究的目的:
- 开发一种新的框架来有效合成受约束的循环四甲.
- 克服循环的挑战,包括表皮化和寡聚化.
主要方法:
- 使用β-thiolactone框架进行直接氨解.
- 采用了一种限制C端碳基旋转的机制,同时保持反应性.
主要成果:
- 成功合成了20多种具有挑战性的循环四甲,高效率.
- 实现了非epimerizable头到尾的化,最大限度地减少了寡合化.
- 合成了以前无法实现的宏循环,包括一种强大的微型阿片类受体激动剂 (EC50 = 2.5 nM).
结论:
- β-thiolactone框架为受约束的循环提供了一个实用的解决方案.
- 这种方法可以合成具有潜在治疗应用的新型循环,例如MOR激动剂.
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