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- Title
Scalable total synthesis of (+)-aniduquinolone A and its acid-catalyzed rearrangement to aflaquinolones.
- Authors
Guo, Feng-Wei; Mou, Xiao-Feng; Qu, Yong; Wei, Mei-Yan; Chen, Guang-Ying; Wang, Chang-Yun; Gu, Yu-Cheng; Shao, Chang-Lun
- Abstract
The strong antibacterial, antiviral and anticancer activities demonstrated by quinolones make them promising lead structures and important synthetic targets for drug discovery. Here, we report, to the best of our knowledge, the first scalable total synthesis of antiviral (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton. This synthetic strategy explores E-stereoselective Horner–Wadsworth–Emmons (HWE) olefination as the key step to assemble isopropenyl substituted tetrahydrofuran onto the 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one core, which is built by highly diastereoselective intramolecular aldol reaction. Moreover, two sets of stereoisomers of aniduquinolone A with substantially overlapping NMR data were synthesized completely and assigned unambiguously by comprehensive analysis of both their spectroscopic and X-ray diffraction data. Unexpectedly, aflaquinolones A, C, and D that feature different 2,4-dimethyl cyclohexanone moieties were transformed successfully from (+)-aniduquinolone A by treating with TFA. The methodology delineated herein can be applied broadly to the synthesis of natural alkaloids containing the core structure of 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one. Quinolones can possess desirable antibacterial, antiviral and anticancer properties, rending them important synthetic targets for drug discovery purposes. Here, the gram-scale total synthesis of antiviral (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton, is reported, as well as its acid-catalyzed rearrangement to aflaquinolones A, C, and D.
- Subjects
SYNTHETIC drugs; ANTINEOPLASTIC agents; QUINOLONE antibacterial agents; X-ray diffraction; STEREOISOMERS; ALDOLS
- Publication
Communications Chemistry, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3669
- Publication type
Article
- DOI
10.1038/s42004-022-00655-x