Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089, USA.
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Org Biomol Chem. 2023 Feb 22;21(8):1667-1673. doi: 10.1039/d2ob01697d.
The total synthesis of Resolvin D4 and its 17()-hydroxy-epimer is reported. These lipid-based natural products are biosynthesized from docosahexaenoic acid (DHA, C22:6) during the body's rapid cellular and chemical response to injurious stimuli and are part of a large class of bioactive molecules that resolve inflammation. Our convergent synthesis employed a chiral pool strategy starting from glycidol derivatives and D-erythrose to introduce stereogenic centers. A copper(I)-mediated cross coupling between propargyl bromide and terminal acetylenic precursors yielded core structures of late-stage key intermediates. A simultaneous Lindlar reduction of the skipped diynyl moiety followed by silyl group cleavage securely completed the synthesis. The synthetic availability of these molecules helped further elucidate their stereoselective biofunctions.
报道了 Resolvin D4 及其 17()-羟基差向异构体的全合成。这些基于脂质的天然产物是在身体对有害刺激的快速细胞和化学反应过程中由二十二碳六烯酸（DHA，C22:6）生物合成的，是一大类具有生物活性的分子的一部分，这些分子可以解决炎症问题。我们的汇聚合成采用了从缩水甘油衍生物和 D-赤藓糖开始的手性池策略来引入手性中心。通过铜（I）介导的丙炔溴和亲核末端炔烃前体之间的交叉偶联反应，得到了晚期关键中间体的核心结构。同时进行 Lindlar 还原消除跳过的二炔基部分，然后进行硅基裂解，可安全地完成合成。这些分子的合成可用性有助于进一步阐明它们的立体选择性生物功能。
