Natural product-like combinatorial libraries based on privileged structures. 2. Construction of a 10 000-membered benzopyran library by directed split-and-pool chemistry using NanoKans and optical encoding

Natural product-like combinatorial libraries based on privileged structures. 2. Construction of a 10 000-membered benzopyran library by directed split-and-pool chemistry using NanoKans and optical encoding
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DOI:
10.1021/ja002034c
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发表时间:
2000-10-18
影响因子:
15
通讯作者:
Lillig, JE
Lillig, JE
中科院分区:
化学1区
文献类型:
--
作者:
Nicolaou, KC;Pfefferkorn, JA;Lillig, JE

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在开发了一种可靠的和通用的固相策略,用于苯并吡喃模板的天然存在的和设计的衍生物的分裂和合并合成(见前一篇论文),我们现在报告用于化学生物学研究的10000元天然产物样化合物库的构建。同时,我们报告了早期应用的IRORI NanoKan光学编码系统的高通量非化学标记和分类库成员在分裂和池合成。文库构建的整体合成策略进行了讨论,并在特定的库成员的背景下,说明反应条件以及产率和纯度的个别反应途径进行了检查,构建块的选择和质量控制的库成员的问题也得到了解决,最后,库化学生物学的潜在应用进行了讨论。
Having developed a reliable and versatile solid-phase strategy for the split-and-pool synthesis of naturally occurring and designed derivatives of the benzopyran template (see preceding paper), we now report the construction of a 10 000-membered natural product-like compound library for chemical biology studies. Concomitantly, we report an early application of the IRORI NanoKan optical encoding system for the high throughput nonchemical tagging and sorting of library members during split-and-pool synthesis. The overall synthetic strategy for library construction is discussed and the individual reaction pathways are examined in the context of specific library members, illustrating reaction conditions as well as yields and purities, The issues of building block selection and quality control of library members are also addressed and, finally, potential applications of the library to chemical biology are discussed.