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

被引:34
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
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
收藏
页码:6763 / 6768
页数:6
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