微粒Brønsted酸介导的DNA标记异环的合成
M Klika Škopić1, K Götte1, C Gramse1
1Faculty of Chemistry and Chemical Biology , TU Dortmund University , Otto-Hahn-Straße 6 , 44227 Dortmund , Germany.
Journal of the American Chemical Society
|June 28, 2019
概括
通过DNA编码的图书馆提供了大量用于药物选的化合物. 聚合物微粒能够在DNA上进行轻微的化学反应,克服局限性并扩展编码化学应用.
科学领域:
- 有机化学
- 聚合物化学
- 医学化学
背景情况:
- 用DNA编码的图书馆 (DEL) 利用分子生物学进行大规模的化合物合成和选.
- 由于排尿,DNA的反应性限制了化学转化,特别是在强酸等恶劣条件下.
- 在温和的,与DNA相容的水性条件下进行化学反应的有希望的策略.
研究的目的:
- 探索基于聚合物的细胞催化剂在DNA编码化学中的应用.
- 通过在聚合物微粒中的温和DNA相容反应来证明各种化学支架的合成.
- 为了适应DEL合成相关的氧化反应的细胞催化.
主要方法:
- 用硫酸部分合成两块共聚物,形成水性.
- 使用这些聚合物微粒作为Povarov和Groebke-Blackburn-Bienaymé反应的纳米反应.
- 应用微粒系统从DNA结合胺中切割三甲基基基 (tBoc) 保护基.
- 对DNA结合醇的铜/双胺/TEMPO介导氧化进行微粒方法的调整.
主要成果:
- 聚合物微粒成功地局部化了布伦斯特酸催化剂,使反应条件温和.
- 通过Povarov和Groebke-Blackburn-Bienaymé反应分别合成了多种替代的四氨基和氨基胺.
- 在微粒条件下实现了tBoc保护组的有效分裂.
- 聚合物系统有效地适应了DNA合醇的氧化.
结论:
- 聚合物基质催化是一种多功能且有效的DNA编码化学策略.
- 这种方法克服了DNA的反应性限制,使更广泛的化学转换成为可能.
- 证明的应用表明聚合物微粒在构建大型DNA编码库中具有广泛的潜力.
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