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- Title
Biocatalytic stereocontrolled head-to-tail cyclizations of unbiased terpenes as a tool in chemoenzymatic synthesis.
- Authors
Schneider, Andreas; Lystbæk, Thomas B.; Markthaler, Daniel; Hansen, Niels; Hauer, Bernhard
- Abstract
Terpene synthesis stands at the forefront of modern synthetic chemistry and represents the state-of-the-art in the chemist's toolbox. Notwithstanding, these endeavors are inherently tied to the current availability of natural cyclic building blocks. Addressing this limitation, the stereocontrolled cyclization of abundant unbiased linear terpenes emerges as a valuable tool, which is still difficult to achieve with chemical catalysts. In this study, we showcase the remarkable capabilities of squalene-hopene cyclases (SHCs) in the chemoenzymatic synthesis of head-to-tail-fused terpenes. By combining engineered SHCs and a practical reaction setup, we generate ten chiral scaffolds with >99% ee and de, at up to decagram scale. Our mechanistic insights suggest how cyclodextrin encapsulation of terpenes may influence the performance of the membrane-bound enzyme. Moreover, we transform the chiral templates to valuable (mero)-terpenes using interdisciplinary synthetic methods, including a catalytic ring-contraction of enol-ethers facilitated by cooperative iodine/lipase catalysis. Terpene synthesis is limited by the current availability of natural cyclic building blocks. In this study, the authors employ squalene-hopene cyclases in the chemoenzymatic synthesis of head-to-tail fused terpenes and generate ten chiral scaffolds with >99% ee and de, at up to decagram scale.
- Subjects
RING formation (Chemistry); CYCLASES; CYCLODEXTRINS; CHEMISTS; BIOCATALYSIS; TERPENES; LIPASES
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-48993-9