Strain-release amination

被引：391

作者：

Gianatassio, Ryan ^{[1
]}

Lopchuk, Justin M. ^{[1
]}

Wang, Jie ^{[1
]}

Pan, Chung-Mao ^{[1
]}

Malins, Lara R. ^{[1
]}

Prieto, Liher ^{[1
]}

Brandt, Thomas A. ^{[2
]}

Collins, Michael R. ^{[3
]}

Gallego, Gary M. ^{[3
]}

Sach, Neal W. ^{[3
]}

Spangler, Jillian E. ^{[3
]}

Zhu, Huichin ^{[3
]}

Zhu, Jinjiang ^{[3
]}

Baran, Phil S. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[2] Pfizer Worldwide Res & Dev, Chem Res & Dev, Groton, CT 06340 USA

[3] Pfizer Inc, La Jolla Labs, Dept Chem, San Diego, CA 92121 USA

来源：

SCIENCE | 2016年 / 351卷 / 6270期

基金：

美国国家卫生研究院;

关键词：

ORGANIC-CHEMISTRY; CLICK CHEMISTRY; DERIVATIVES; BIOCONJUGATION; POTENT; FUNCTIONALIZATION; MACROCYCLIZATION; HETEROCYCLES; BRIDGEHEAD; DESIGN;

D O I：

10.1126/science.aad6252

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

To optimize drug candidates, modern medicinal chemists are increasingly turning to an unconventional structural motif: small, strained ring systems. However, the difficulty of introducing substituents such as bicyclo[1.1.1]pentanes, azetidines, or cyclobutanes often outweighs the challenge of synthesizing the parent scaffold itself. Thus, there is an urgent need for general methods to rapidly and directly append such groups onto core scaffolds. Here we report a general strategy to harness the embedded potential energy of effectively spring-loaded C-C and C-N bonds with the most oft-encountered nucleophiles in pharmaceutical chemistry, amines. Strain-release amination can diversify a range of substrates with a multitude of desirable bioisosteres at both the early and late stages of a synthesis. The technique has also been applied to peptide labeling and bioconjugation.

引用

页码：241 / 246

页数：6

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