Divergent Synthesis of Complex Diterpenes via a Hybrid Oxidative Approach

• Published in: Science (American Association for the Advancement of Science) 2020-08, Vol.369 (6505), p.799-806
• Main Authors: Zhang, Xiao, King-Smith, Emma, Dong, Liao-Bin, Yang, Li-Cheng, Rudolf, Jeffrey D., Shen, Ben, Renata, Hans
• Format: Article
• Language: English
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abb8271

Polycyclic diterpenes exhibit many important biological activities, but de novo synthetic access to these molecules is highly challenging due to their structural complexity. Semisynthetic access has also been limited by the lack of chemical tools for scaffold modifications. We report a chemoenzymatic platform to access highly oxidized diterpenes by a hybrid oxidative approach that strategically combines chemical and enzymatic oxidation methods. This approach allows for selective oxidations of previously inaccessible sites on the parent carbocycles and enables abiotic skeletal rearrangements to additional underlying architectures. We synthesized a total of nine complex natural products with rich oxygenation patterns and skeletal diversity in ten steps or less from ent -steviol. Synthesis of nine complex diterpenes through combined chemical and enzymatic C–H oxidation methods.