Trifluoromethylation of Antimycin via Extender Unit Incorporation Improves Antifungal Potency
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Updated: Jul 18, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Jun Zhang1,2,3, Qian Yun1,3, Yuhan Dai2,3
1School of Pharmacy, Fudan University, 826 Zhangheng Rd., Shanghai 201203, China.
Abstract:
We report the first biosynthesis of trifluoromethyl (TFM)-containing extender unit and its incorporation into the polyketide biosynthetic pathway. Using engineered enzymes UkaQFAV and Arm13-ACCase, we synthesized a TFM-containing extender unit, which was successfully integrated into the antimycin structure. This modification resulted in stereochemical changes, leading to the formation of an unusual 7S-epimer. The TFM-modified antimycin derivatives exhibited significantly enhanced antifungal activity, providing a new strategy for polyketide diversification and drug development.
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