Bielecki Michael, Nassir Molhm, Sharma Hayden A, Truax Nathanyal J, Raheja Nicholas, Thompson Ty M, El-Hayek Ewing Tamara, Melillo Bruno, Cravatt Benjamin F, Baran Phil S
Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Vividion Therapeutics, San Diego, California 92121, United States.
J Am Chem Soc. 2025 Jun 25;147(25):22209-22218. doi: 10.1021/jacs.5c07227. Epub 2025 Jun 11.
A simple, modular, and programmable approach to access complex stereopure azetidines through strain-release functionalization is disclosed. The synthetic methods developed enable the parallel synthesis of stereodefined azetidines that would be otherwise laborious to produce. Given the privileged nature of these structures, a set of stereoprobes for use in activity-based protein profiling was prepared and evaluated, revealing proteins in human cancer cells, which were liganded with clear stereo- and chemo-selectivity.
公开了一种通过应变释放功能化来获取复杂立体纯氮杂环丁烷的简单、模块化且可编程的方法。所开发的合成方法能够并行合成立体定向的氮杂环丁烷，否则其制备过程会很繁琐。鉴于这些结构的特殊性质，制备并评估了一组用于基于活性的蛋白质谱分析的立体探针，揭示了人类癌细胞中以明确的立体和化学选择性进行配体结合的蛋白质。
