Structural and stereochemical diversity in prenylated indole alkaloids containing the bicyclo[2.2.2]diazaoctane ring system from marine and terrestrial fungi

Kimberly R Klas, Hikaru Kato, Jens C. Frisvad, Fengan Yu, Sean A. Newmister, Amy E. Fraley, David H. Sherman, Sachiko Tsukamoto, Robert M. Williams*

*Corresponding author for this work

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Abstract

Covering: up to February 2017
Various fungi of the genera Aspergillus, Penicillium, and Malbranchea produce prenylated indole alkaloids possessing a bicyclo[2.2.2]diazaoctane ring system. After the discovery of distinct enantiomers of the natural alkaloids stephacidin A and notoamide B, from A. protuberus MF297-2 and A. amoenus NRRL 35660, another fungi, A. taichungensis, was found to produce their diastereomers, 6-epi-stephacidin A and versicolamide B, as major metabolites. Distinct enantiomers of stephacidin A and 6-epi-stephacidin A may be derived from a common precursor, notoamide S, by enzymes that form a bicyclo[2.2.2]diazaoctane core via a putative intramolecular hetero-Diels-Alder cycloaddition. This review provides our current understanding of the structural and stereochemical homologies and disparities of these alkaloids. Through the deployment of biomimetic syntheses, whole-genome sequencing, and biochemical studies, a unified biogenesis of both the dioxopiperazine and the monooxopiperazine families of prenylated indole alkaloids constituted of bicyclo[2.2.2]diazaoctane ring systems is presented.
Original languageEnglish
JournalNatural Product Reports
Volume35
Issue number6
Pages (from-to)532-558
Number of pages27
ISSN0265-0568
DOIs
Publication statusPublished - 2018

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