Divergent Synthesis of Complex Diterpenes via a Hybrid Oxidative Approach

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 chemoenzymati...

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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
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container_issue 6505
container_start_page 799
container_title Science (American Association for the Advancement of Science)
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creator Zhang, Xiao
King-Smith, Emma
Dong, Liao-Bin
Yang, Li-Cheng
Rudolf, Jeffrey D.
Shen, Ben
Renata, Hans
description 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.
doi_str_mv 10.1126/science.abb8271
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title Divergent Synthesis of Complex Diterpenes via a Hybrid Oxidative Approach
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