Ruthenium Promoted On-DNA Ring-Closing Metathesis and Cross-Metathesis

被引：73
作者：
Lu, Xiaojie [1 ]
Fan, Lijun [1 ]
Phelps, Christopher B. [1 ]
Davie, Christopher P. [1 ]
Donahue, Christine P. [1 ]
机构：
[1] GlaxoSmithKline, Platform Technol & Sci Drug Discovery & Select, New Chem Ent Mol Discovery, Encoded Lib Technol, 830 Winter St, Waltham, MA 02451 USA
来源：
BIOCONJUGATE CHEMISTRY | 2017年 / 28卷 / 06期
关键词：
ENCODED CHEMICAL LIBRARIES; SMALL-MOLECULE LIBRARIES; OLEFIN-METATHESIS; NOBEL LECTURE; DISCOVERY; INHIBITORS; SELECTION; CATALYSTS; RECEPTOR; POTENT;
D O I：
10.1021/acs.bioconjchem.7b00292
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
DNA-encoded library technology (ELT) is now widely used in pharmaceutical, biotechnological, and academic research for hit identification and target validation. New on-DNA reactions are keys to exploring greater chemical space and accessing challenging chemotypes such as configurationally constrained macrocycles. Herein, we describe the first on-DNA ring closing metathesis (RCM) and cross-metathesis (CM) reactions promoted by fast initiating Grubbs Ru reagents. Under the optimized conditions, MgCl2 was used to protect the DNA from Ru-induced decomposition. The substrate scope for on-DNA RCM was established and the same conditions were applied to a CM reaction with good conversion.
引用
收藏
页码：1625 / 1629
页数：5
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