Synthesis of a Stereochemically Diverse Library of Medium-Sized Lactams and Sultams via SNAr Cycloetherification
Synthesis of a Stereochemically Diverse Library of Medium-Sized Lactams and Sultams via SNAr Cycloetherification
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DOI：
10.1021/co2000218
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发表时间：
2011-07-01
影响因子：
--
通讯作者：
Marcaurelle, Lisa A.
中科院分区：
文献类型：
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作者：
Gerard, Baudouin;Duvall, Jeremy R.;Marcaurelle, Lisa A.
我们为 StereocherniCally 的 Sinksil 实施了基于羟醛的“构建/耦合/配对”(B/C/P) 策略。多种 8 元内酰胺和磺内酰胺支架：通过 SNAr 环醚化。每个支架包含两个手柄，一个胺和一个芳基溴，通过 N 封端和 Pd 介导的交叉偶联实现固相多样化。实施了稀疏矩阵设计策略，实现了控制理化性质和选择不同文库成员的双重目标。讨论了两个 8000 成员文库的生成，包括对文库纯度和特性分布的全面分析。通过使用多重融合相似性 (MFS) 图和主成分分析 (PCA)，与分子库小分子存储库 (MLSMR) 进行比较，评估文库多样性。
We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the Sinksil of SterreocherniCally. diverse 8-membered lactam and sultam Scaffolds: via SNAr cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd mediated cross coupling. A sparse matrix design strategy that achieves the dual objective of controlling physicochemical properties and selecting diverse library members was implemented. The.production of two 8000-membered libraries is discussed including a full analysis of library purity and property distribution. Library diversity was evaluated in comparison to the Molecular Library Small Molecule Repository (MLSMR) through the use of a multifusion similarity (MFS) map and principal component analysis (PCA).