Biosynthesis of Piperazine-Derived Diazabicyclic Alkaloids Involves a Nonribosomal Peptide Synthetase and Subsequent Tailoring by a Multifunctional Cytochrome P450 Enzyme

Piperazine-derived diazabicycles are privileged structures found in natural products and synthetic chemical entities, including therapeutic agents. Herein, we deciphered the biosynthesis of two unique classes of diazabicyclic alkaloids, fischerazines A–C. Notably, we characterized a multifunctional...

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Published in:Organic letters 2022-06, Vol.24 (22), p.4064-4069
Main Authors: Pham, Mai-Truc, Chen, Shu-Rong, Liang, Suh-Yuen, Cheng, Yuan-Bin, Lin, Hsiao-Ching
Format: Article
Language:English
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Summary:Piperazine-derived diazabicycles are privileged structures found in natural products and synthetic chemical entities, including therapeutic agents. Herein, we deciphered the biosynthesis of two unique classes of diazabicyclic alkaloids, fischerazines A–C. Notably, we characterized a multifunctional P450 monooxygenase NfiC that installs ortho-dihydroxyl groups on the dibenzyl-piperazines, in turn triggering a range of NfiC-catalyzed and spontaneous cyclization events.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.2c01516