Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification.
Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification.
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通过连续的多组分组装过程、环化和多样化制备生物活性小分子的策略的演变。
DOI：
10.1039/c4ob00835a
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发表时间：
2014
影响因子：
3.2
通讯作者：
Martin,StephenF
中科院分区：
文献类型：
--
作者：
Sahn,JamesJ;Granger,BrettA;Martin,StephenF
一种产生不同小分子集合的策略已经开发出来，其特点是多组分组装过程（MCAP），以有效地构建具有芳基氨基甲基亚基的各种中间体。然后，这些关键化合物通过选择性成环反应转化为杂环支架，每个杂环支架都具有适合进一步衍生化和钯催化交叉偶联反应的功能手柄。这种方法的模块化特性使构建具有广泛取代基和取代模式的多环化合物文库变得容易，从而用于生物学评价。由此产生的几种化合物文库的筛选揭示了大量具有广谱医学相关活性的化合物。
A strategy for generating diverse collections of small molecules has been developed that features a multicomponent assembly process (MCAP) to efficiently construct a variety of intermediates possessing an aryl aminomethyl subunit. These key compounds are then transformed via selective ring-forming reactions into heterocyclic scaffolds, each of which possesses suitable functional handles for further derivatizations and palladium-catalyzed cross coupling reactions. The modular nature of this approach enables the facile construction of libraries of polycyclic compounds bearing a broad range of substituents and substitution patterns for biological evaluation. Screening of several compound libraries thus produced has revealed a large subset of compounds that exhibit a broad spectrum of medicinally-relevant activities.