简化SuFEx抑制剂开发:采用光性和正对角硫酸盐保护组的统一方法
Twinkle I Patel1, Makayla L Williams1, Yumeng Chi1
1Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, 163 Frelinghuysen Road, Piscataway, New Jersey, USA.
Angewandte Chemie (International ed. in English)
|April 22, 2025
概括
新的硫酸盐保护基 (SPG) 增强了硫烯化物 (SFs) 的稳定性和合成效用. 这些新型的光性SPG能够在药物发现和生物化学中实现后期功能化.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 化学生物学 化学生物学
背景情况:
- 硫烯化物 (SFs) 由于其点击反应特性,在药物发现和生物化学中至关重要.
- 合成不稳定性和晚期引入限制了含SF分子的多样性.
- 现有的硫酸盐保护组 (SPG) 的稳定性有限,阻碍了更广泛的应用.
研究的目的:
- 发现和选择具有更好的稳定性和合成可访问性的新型硫酸盐保护组 (SPG).
- 开发可以轻松与烯化物合并轻松解除保护的SPG.
- 为了证明这些SPG在合成各种生物活性小分子中的实用性.
主要方法:
- 基于稳定性,容易合成和去保护条件的SPG的选和选择.
- 新型光性SPG的合成:帕-甲基罗加和正基罗加.
- 在各种合成条件下评估SPG稳定性及其与化的合.
- 将含有SPG的构建块纳入生物活性小分子.
主要成果:
- 发现了两种新型的光性SPG:帕-甲基罗加和正-尼托罗加.
- 在共同的合成条件下,这些SPG与2-trimethylsilylethyl sulfone (SES) 一起表现出广泛的稳定性.
- 从硫酸盐前体中成功将SPG与烯化物合起来.
- 在合成含有SPG的生物活性分子的构建块中显示的实用性.
结论:
- 开发了强大而多功能的SPG,克服了现有方法的局限性.
- 能够在后期引入具有增强结构多样性的硫尼尔化物部分.
- 通过改进的合成策略,促进了新型生物活性小分子的合成.
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