Creation and manipulation of common functional groups en route to a skeletally diverse chemical library
Creation and manipulation of common functional groups en route to a skeletally diverse chemical library
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DOI：
10.1073/pnas.1015253108
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发表时间：
2011-04-26
影响因子：
11.1
通讯作者：
Kozmin, Sergey A.
中科院分区：
文献类型：
--
作者：
Cui, Jiayue;Hao, Jason;Kozmin, Sergey A.
我们开发了一种有效的策略来构建骨架多样化的化学库，其中需要一系列烯炔环异构化、[4 + 2]环加成、烯烃二羟基化和二醇氨甲酰化。使用这种方法，只需要 16 个容易获得的构建模块即可生成具有代表性的 191 个成员的文库，该文库显示出广泛的分子形状分布和优异的理化性质。该文库进一步鉴定了一种小分子，该小分子可有效抑制 CHO-K1 细胞系中 ATP 和乳酸的糖酵解产生，为开发新型糖酵解抑制剂提供了潜在的先导。
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.