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Updated: Oct 25, 2026

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Chemoenzymatic Synthesis of (E,E,Z)-Humulene-Derived Natural Products
Anthony T Saucedo1,2, Brian Valladares1,2, David A Delgadillo3
1Life Sciences Institute, University of Michigan, Ann Arbor, Michigan48109, United States.
Abstract:
Meroterpenoid natural products derived from the 11-membered macrocycle humulene are of great interest due to their potent biological activities and intricate architectures. Whereas molecules derived from the most available (E,E,E)-humulene isomer have been thoroughly investigated, little is known of the chemistry and biological properties of natural products derived from the (E,E,Z)-isomer and derivatives thereof. Herein, we detail the first synthesis of (E,E,Z)-(10S)-hydroxyhumulene through a selective oxidative double-bond isomerization, and using this key building block along with (E,E,Z)-humulene, a suite of complex meroterpenoids was synthesized, including (±)-deoxynoreupenifeldin and neosetophomone B through a chemoenzymatic strategy and pughiinin A through a non-enzymatic route. In addition to gaining synthetic access to a suite of (E,E,Z)-humulene-derived natural products, this work revealed reactivity differences between (E,E,E)-humulene and its (E,E,Z)-isomer. Overall, these efforts culminate in the first total syntheses of three (E,E,Z)-humulene-derived natural products, providing access to this untapped subset of secondary metabolites.
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