Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs and Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China.
Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai 200240, China.
J Am Chem Soc. 2024 Sep 25;146(38):26243-26250. doi: 10.1021/jacs.4c07956. Epub 2024 Sep 14.
In nature, basic terpene skeletons are produced and subsequently undergo enzymatic or nonenzymatic oxidative transformations, leading to diverse structural variations. To date, thousands of natural products featuring a variety of oxidation patterns have been isolated solely from the labdane family. This work describes a strategy for the comprehensive introduction of oxidation states into the labdane core by employing a combination of enzyme library screening, directed evolution, and sequential chemical oxidation processes. Furthermore, we showcase the functional viability of our chemoenzymatic approach by accomplishing a formal synthesis of nimbolide, highlighting its potential for streamlining the synthesis of complex natural products.
在自然界中，基本的萜烯骨架被产生，然后经历酶或非酶氧化转化，导致结构的多样性变化。迄今为止，仅从 labdane 家族中就分离出了成千上万具有各种氧化模式的天然产物。这项工作描述了一种通过酶文库筛选、定向进化和顺序化学氧化过程相结合，在 labdane 核中全面引入氧化态的策略。此外，我们通过完成 nimbolide 的全合成，展示了我们的化学酶法方法的功能可行性，突出了其简化复杂天然产物合成的潜力。
