Flavanols are privileged heterocyclic compounds in medicinal chemistry. It is notable to develop an efficient and straightforward protocol for accessing chiral flavanols with precise control of the stereocenters. Here, a highly efficient kinetic resolution of chromenes was reported via Cu-catalyzed asymmetric hydroboration. This previously unidentified approach features a one-step synthesis of chiral flavan-3-ols containing two vicinal stereogenic centers via a highly efficient kinetic resolution ( s factor up to 1060, >99% ee for most products). In addition, the anti-inflammation effects of these diversified flavan-3-ols were studied by the in vitro experiments and RNA sequencing analysis. These flavan-3-ols showed inhibitory effects on the secretion of pro-inflammation cytokines including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor–α (TNF-α), as well as inhibiting the inflammation responses through down-regulating the gene transcriptions closely related to PI3K-Akt signaling pathway and TNF signaling pathway. The results suggested that these newly synthesized flavan-3-ols have the potential to be lead compounds for anti-inflammatory drugs.

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铜催化色烯动力学拆分不对称合成黄烷醇及其抗炎活性

黄烷醇是药物化学中的特殊杂环化合物。值得注意的是，开发了一种有效且直接的协议，用于通过精确控制立体中心来获取手性黄烷醇。在这里，通过铜催化的不对称硼氢化报道了色烯的高效动力学拆分。这种以前未知的方法的特点是通过高效的动力学拆分一步合成含有两个邻位立体中心的手性黄烷-3-醇。s系数高达 1060，对于大多数产品 > 99% ee）。此外，通过体外实验和RNA测序分析研究了这些多样化的flavan-3-ols的抗炎作用。这些黄烷-3-醇对促炎细胞因子的分泌具有抑制作用，包括白细胞介素-1β (IL-1β)、IL-6 和肿瘤坏死因子-α (TNF-α)，以及抑制炎症反应通过下调与PI3K-Akt信号通路和TNF信号通路密切相关的基因转录。结果表明，这些新合成的flavan-3-ols有可能成为抗炎药的先导化合物。