开发用于DNA编码图书馆合成的本佐福在DNA上的形成
Ayun Luo1, Hongxia Zhou1, Xiuming Wang1
1Pharmaron (Ningbo) Technology Development Co., Ltd., No. 800 Bin-Hai fourth Road, Hangzhou Bay New Zone, Ningbo 315336, P. R. China.
Organic letters
|February 22, 2024
概括
一种新的方法在DNA上使用化物合成佐. 这种强大的方法使得DNA编码的库合成了多样化,医学上重要的福支架.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 合成化学 合成化学
背景情况:
- 福的支架在制药中很常见.
- 对于药物发现而言,各种福库的高效合成至关重要.
- DNA编码图书馆 (DEL) 技术为选大型化学空间提供了一个强大的平台.
研究的目的:
- 开发一种新的,高效的方法,用于在DNA上合成松支架.
- 为了利用独特的级联反应来构建各种基于佐的库.
- 扩大DNA编码库合成的实用性,以获取药物相关化合物.
主要方法:
- 设计了一种新的同质化-异环化级联反应.
- 该方法利用Seyferth-Gilbert同质化,然后在现场进行Sonogashira合和分子内循环.
- 反应序列被优化为在DNA支上进行一两步执行.
主要成果:
- 从易于获得的化物中成功地在DNA上合成了佐.
- 开发的级联反应表明了高产量和广泛的基质范围.
- 通过DNA编码图书馆合成产生了各种各样的与药学相关的福支架.
结论:
- 新型的同质化-异环化级联为DEL合成提供了强大而独特的途径.
- 这种方法显著扩大了可访问的化学空间,用于基于佐的药物发现.
- 开发的DNA合成方法为医学上重要的支架提供了一条有效的途径.
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