Enzymatic Intermolecular Hetero-Diels-Alder Reaction in the Biosynthesis of Tropolonic Sesquiterpenes.

Abstract

Diels-Alder reactions are among the most powerful synthetic transformations to construct complex natural products. Despite that increasing of enzymatic intramolecular Diels-Alder reactions have been discovered, natural intermolecular Diels-Alderases are rarely described. Here, we report an intermolecular hetero-Diels-Alder reaction in the biosynthesis of tropolonic sesquiterpenes and functionally characterize EupfF as the first fungal intermolecular hetero-Diels-Alderase. We demonstrate that EupfF catalyzed the dehydration of a hydroxymethyl-containing tropolone (5) to generate a reactive tropolone o-quinone methide (6) and might further stereoselectively control the subsequent intermolecular hetero-Diels-Alder reaction with (1E,4E,8Z)-humulenol (8) to produce enantiomerically pure neosetophomone B (1). Our results reveal the biosynthetic pathway of 1 and expand the repertoire of activities of Diels-Alder cyclases.

• Authors: Qibin Chen, Jie Gao, Cooper Jamieson, Jiawang Liu, Masao Ohashi, Jian Bai, Daojian Yan, Bingyu Liu, Yongsheng Che, Yanan Wang, K N Houk, Youcai Hu
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 141 Issue 36 Pg. 14052-14056 (09 11 2019) ISSN: 1520-5126 [Electronic] United States
• PMID: 31461283 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Fungal Proteins
• Sesquiterpenes
• Methyltransferases

Topics

• Cycloaddition Reaction
• Fungal Proteins (chemistry, metabolism)
• Methyltransferases (chemistry, metabolism)
• Molecular Conformation
• Sesquiterpenes (chemistry, metabolism)