磺酰
多样性(政治)
化学
药效团
组合化学
氟化物
立体化学
有机化学
社会学
人类学
无机化学
烷基
作者
Christopher J. Smedley,Gencheng Li,Andrew S. Barrow,Timothy L. Gialelis,Marie‐Claire Giel,Alessandra Ottonello,Yunfei Cheng,Seiya Kitamura,Dennis W. Wolan,K. Barry Sharpless,John E. Moses
标识
DOI:10.1002/anie.202003219
摘要
Abstract Diversity Oriented Clicking (DOC) is a unified click‐approach for the modular synthesis of lead‐like structures through application of the wide family of click transformations. DOC evolved from the concept of achieving “diversity with ease” , by combining classic C−C π‐bond click chemistry with recent developments in connective SuFEx‐technologies. We showcase 2‐ S ubstituted‐ A lkynyl‐1‐ S ulfonyl F luorides (SASFs) as a new class of connective hub in concert with a diverse selection of click‐cycloaddition processes. Through the selective DOC of SASFs with a range of dipoles and cyclic dienes, we report a diverse click‐library of 173 unique functional molecules in minimal synthetic steps. The SuFExable library comprises 10 discrete heterocyclic core structures derived from 1,3‐ and 1,5‐dipoles; while reaction with cyclic dienes yields several three‐dimensional bicyclic Diels–Alder adducts. Growing the library to 278 discrete compounds through late‐stage modification was made possible through SuFEx click derivatization of the pendant sulfonyl fluoride group in 96 well‐plates—demonstrating the versatility of the DOC approach for the rapid synthesis of diverse functional structures. Screening for function against MRSA (USA300) revealed several lead hits with improved activity over methicillin.
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