Chemoenzymatic Oxidation\nof Labdane and Formal Synthesis\nof Nimbolide

In nature, basic terpene skeletons are produced and subsequently\nundergo enzymatic or nonenzymatic oxidative transformations, leading\nto diverse structural variations. To date, thousands of natural products\nfeaturing a variety of oxidation patterns have been isolated solely\nfrom the labdane family. This work describes a strategy for the comprehensive\nintroduction of oxidation states into the labdane core by employing\na combination of enzyme library screening, directed evolution, and\nsequential chemical oxidation processes. Furthermore, we showcase\nthe functional viability of our chemoenzymatic approach by accomplishing\na formal synthesis of nimbolide, highlighting its potential for streamlining\nthe synthesis of complex natural products.