在构建具有丰富骨架多样性的化学库的过程中，创造和操作常见的功能基团。
Creation and manipulation of common functional groups en route to a skeletally diverse chemical library.
机构信息
Chicago Tri-Institutional Center for Chemical Methods and Library Development, Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
出版信息
Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):6763-8. doi: 10.1073/pnas.1015253108. Epub 2011 Mar 7.
Abstract
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.
摘要
我们开发了一种高效的骨架多样性化学文库的构建策略，该策略包括一系列烯炔环异构化、[4+2]环加成、烯烃双羟化和二醇氨甲酰化反应。使用这种方法，仅需 16 个易得的构建块就可以生成具有代表性的 191 成员文库，该文库展示了广泛的分子形状分布和优异的物理化学性质。这个文库进一步鉴定出了一种小分子，它可以有效地抑制 CHO-K1 细胞系中的糖酵解产生 ATP 和乳酸，代表了一类新型糖酵解抑制剂的潜在先导化合物。
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本文引用的文献
1
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Angew Chem Int Ed Engl. 2001 Nov 19;40(22):4274-4277. doi: 10.1002/1521-3773(20011119)40:22<4274::AID-ANIE4274>3.0.CO;2-#.
2
A synthesis of substituted pyrrolidines via a palladium(2+)-catalyzed cyclization. An unusual approach to a carbapenem.通过钯（II）催化环化合成取代吡咯烷。一种合成碳青霉烯的非常规方法。
J Am Chem Soc. 1986 Sep 1;108(19):6053-4. doi: 10.1021/ja00279a071.
3
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Chem Biol. 2011 Feb 25;18(2):222-30. doi: 10.1016/j.chembiol.2010.12.015.
4
Stereochemical and skeletal diversity arising from amino propargylic alcohols.手性和骨架多样性源于氨基丙炔醇。
Org Lett. 2010 Jun 18;12(12):2822-5. doi: 10.1021/ol100914b.
5
Understanding the Warburg effect: the metabolic requirements of cell proliferation.理解瓦伯格效应：细胞增殖的代谢需求。
Science. 2009 May 22;324(5930):1029-33. doi: 10.1126/science.1160809.
6
Design and synthesis of a library of tetracyclic hydroazulenoisoindoles.四环氢化薁并异吲哚类化合物库的设计与合成。
J Comb Chem. 2009 May-Jun;11(3):486-94. doi: 10.1021/cc900024p.
7
Gold(I)-catalyzed coupling reactions for the synthesis of diverse small molecules using the build/couple/pair strategy.使用构建/偶联/配对策略，金（I）催化的用于多种小分子合成的偶联反应。
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8
Synthesis of natural-product-like molecules with over eighty distinct scaffolds.具有八十多种不同骨架的类天然产物分子的合成。
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9
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10
Cycloisomerization of 1,n-enynes: challenging metal-catalyzed rearrangements and mechanistic insights.1,n-烯炔的环异构化：具有挑战性的金属催化重排及机理见解
Angew Chem Int Ed Engl. 2008;47(23):4268-315. doi: 10.1002/anie.200701589.
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