Generation of Unusual Aromatic Polyketides by Incorporation of Phenylamine Analogues into a C-Ring-Cleaved Angucyclinone

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 7; p. 1959
• Main Authors: Xiao, Hua, Wang, Guiyang, Wang, Zhengdong, Kuang, Yi, Song, Juan, Jin, Jing, Ye, Min, Yang, Donghui, Ma, Ming
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.03.2021; MDPI
• Subjects: angucyclinones; Anthracene; Biosynthesis; Conversion; disubstituted phenylamines; Experiments; Fermentation; Natural products; nonenzymatic conversion; Nrf2 transcription activation; Polyketides; Spectrum analysis; Streptomyces; United States > US; disubstituted phenylamines; nonenzymatic conversion; angucyclinones; Nrf2 transcription activation
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26071959

Angucyclinones are aromatic polyketides that possess impressive structural diversity and significant biological activities. The structural diversity of these natural products is attributed to various enzymatic or nonenzymatic modifications on their tetracyclic benz( )anthracene skeleton. Previously, we discovered an unusual phenylamine-incorporated angucyclinone ( ) from a marine sp. PKU-MA00218, and identified that it was produced from the nonenzymatic conversion of a C-ring-cleaved angucyclinone ( ) with phenylamine. In this study, we tested the nonenzymatic conversion of with more phenylamine analogues, to expand the utility of this feasible conversion in unusual angucyclinones generation. The (3-ethynyl)phenylamine and disubstituted analogues including (3,4-dimethyl)phenylamine, (3,4-methylenedioxy)phenylamine, and (4-bromo-3-methyl)phenylamine were used in the conversion of , which was isolated from the fermentation of sp. PKU-MA00218. All four phenylamine analogues were incorporated into efficiently under mild conditions, generating new compounds - . The activation of - on nuclear factor erythroid 2-related factor 2 (Nrf2) transcription were tested, which showed that possessing a dimethyl-substitution gave most potent activity. These results evidenced that disubstitutions on phenylamine can be roughly tolerated in the nonenzymatic reactions with , suggesting extended applications of more disubstituted phenylamines incorporation to generate new bioactive angucyclinones in the future.