Creation and manipulation of common functional groups en route to a skeletally diverse chemical library

被引：35

作者：

Cui, Jiayue ^{[1
,2
]}

Hao, Jason ^{[1
,2
]}

Ulanovskaya, Olesya A. ^{[1
,2
]}

Dundas, Joseph ^{[1
,3
]}

Liang, Jie ^{[1
,3
]}

Kozmin, Sergey A. ^{[1
,2
]}

机构：

[1] Univ Chicago, Chicago Triinst Ctr Chem Methods & Lib Dev, Chicago, IL 60637 USA

[2] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

[3] Univ Illinois, Dept Bioengn, Chicago, IL 60607 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 17期

基金：

美国国家卫生研究院;

关键词：

diversity-oriented synthesis; glycolysis; skeletal diversity; ASYMMETRIC AMINOHYDROXYLATION; TRANSITION-METALS; DRUG DISCOVERY; CYCLOISOMERIZATION; CYCLIZATION; METATHESIS; STRATEGY; GOLD; CYCLOHEXADIENES; N-ENYNES;

D O I：

10.1073/pnas.1015253108

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：

We have developed an efficient strategy to a skeletally diverse chemical library, which entailed a sequence of enyne cycloisomerization, [4 + 2] cycloaddition, alkene dihydroxylation, and diol carbamylation. Using this approach, only 16 readily available building blocks were needed to produce a representative 191-member library, which displayed broad distribution of molecular shapes and excellent physicochemical properties. This library further enabled identification of a small molecule, which effectively suppressed glycolytic production of ATP and lactate in CHO-K1 cell line, representing a potential lead for the development of a new class of glycolytic inhibitors.

引用

页码：6763 / 6768

页数：6

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