Chemoenzymatic Oxidation of Labdane and Formal Synthesis of Nimbolide
Xiaotao Liu1, Yaoyao Xu1, Lingling Li2
1Frontiers 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.
Abstract:
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.
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