Stereocontrolled synthesis of a complex library via elaboration of angular epoxyquinol scaffolds
Stereocontrolled synthesis of a complex library via elaboration of angular epoxyquinol scaffolds
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DOI：
10.1021/jo050956y
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发表时间：
2005-08-05
影响因子：
3.6
通讯作者：
Porco, JA
中科院分区：
文献类型：
--
作者：
Lei, XG;Zaarur, N;Porco, JA
我们已经完成了合成一个复杂的化学文库，通过精心制作具有不同骨架框架的角环氧喹啉支架。关键策略是通过手性非外消旋环氧喹啉二烯的高度立体控制[4 + 2]diols - alder环加成来生成支架。进一步的支架多样化包括氢化、外映化、脱水和羰基与烷氧胺和氨基甲酸酯构建块的缩合。通过羟基定向Diels-Alder环加成和还原性N-N键裂解，进一步完善支架还提供了新的骨架框架。整个过程产生了244个高度复杂和功能化的化合物。对文库进行初步的生物学筛选，发现6个化合物对Hsp 72的诱导有明显的抑制作用。
We have accomplished the synthesis of a complex chemical library via elaboration of angular epoxyquinol scaffolds with distinct skeletal frameworks. The key strategy involves highly stereocontrolled [4 + 2] Diels-Alder cycloadditions of chiral, nonracemic epoxyquinol dienes to generate the scaffolds. Further scaffold diversification involves hydrogenation, epimerization, dehydration, and condensation of the carbonyl group with alkoxyamine and carbazate building blocks. Further elaboration of the scaffolds also provided new skeletal frameworks using hydroxyl-directed Diels-Alder cycloaddition and reductive N-N bond cleavage. The overall process afforded 244 highly complex and functionalized compounds. Preliminary biological screening of the library uncovered six compounds which showed significant inhibition of Hsp 72 induction.