2 - - 胺乙基组 - - 一种用于寡核酸合成的新型酸盐保护基
1Department of Medicinal Chemistry, Isis Pharmaceuticals, Inc., 2292 Faraday Ave., Carlsbad, California 92009, USA. aguzaev@isisph.com
Journal of the American Chemical Society
|July 18, 2001
概括
针对寡核酸合成的新型胺保护组提供可调节的降低保护率,其中一些可以在几分钟内去除. 这使得天然和改性寡核酸的高效合成能够在不损坏核酸的情况下进行.
科学领域:
- 有机化学 有机化学
- 核酸化学的核酸化学
- 合成化学 合成化学
背景情况:
- 有效合成寡核酸需要强大的保护群策略.
- 现有的胺保护组表现出可变的稳定性和降低保护的动力学.
- 需要新的保护组来优化寡核酸合成.
研究的目的:
- 合成和评估具有P(III) 保护的新型5'-O-(4,4'-dimethoxytrityl) 提米丁光胺基.
- 研究这些新型保护群体的降低保护动力学和机制.
- 评估这些构建块在合成寡核酸及其类似物中的实用性.
主要方法:
- 合成了11种新型的2 - 胺乙醇保护酸.
- 这些胺酸盐的纳入合成的20-米尔寡核酸和酸类型.
- 使用缩氧化在不同温度下降低保护的动力学研究.
- 使用模型三,对去保护过程的机械研究.
主要成果:
- 解除保护的时间从25分钟到48小时不等,这取决于保护组的替代模式.
- 2-[N-异烯-N-(4-甲基) 氨基]乙基 (H) 和欧米茄-基 (I和K) 组显示了最快的去除.
- 合成了新的化试剂和胺基构建块,并在寡核酸合成中成功应用.
- 脱保护机制揭示了pH值独立的稳定二氧化离子中间体的形成,该中间体不会与寡核酸反应.
结论:
- 开发了一种多功能战略,用于保护核酸间二基组.
- 新型保护组提供可调节的降低保护率,使高效的寡核酸合成成为可能.
- 这种方法在合成有机化学中具有应用潜力,涉及 (III) 和 (V) 化合物.
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