基于功能和模块化的（±）-顺式-伪愈创木内酯合成：新型 Nrf2 激活剂和 NF-κB 抑制剂的发现。
Function-Oriented and Modular (+/-)-cis-Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF-κB Inhibitors.
机构信息
Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL, 32608, USA.
Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL, 32610, USA.
出版信息
Chemistry. 2021 Mar 22;27(17):5564-5571. doi: 10.1002/chem.202100038. Epub 2021 Feb 26.
Abstract
Described herein is a function-oriented synthesis route and biological evaluation of pseudoguaianolide analogues. The 10-step synthetic route developed retains the topological complexity of the natural product, installs functional handles for late-stage diversification, and forges the key bioactive Michael acceptors early in the synthesis. The analogues were found to be low-micromolar Nrf2 activators and micromolar NF-κB inhibitors and dependent on the local environment of the Michael acceptor moieties.
摘要
本文描述了一种伪愈创木烷型倍半萜类似物的基于功能的合成路线和生物评价。所开发的 10 步合成路线保留了天然产物的拓扑复杂性，为后期多样化安装功能手柄，并在合成早期锻造关键的生物活性迈克尔受体。这些类似物被发现是低微摩尔 Nrf2 激活剂和微摩尔 NF-κB 抑制剂，并依赖于迈克尔受体部分的局部环境。
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