Scalable total synthesis of (+)-aniduquinolone A and its acid-catalyzed rearrangement to aflaquinolones

• DOI: 10.1038/s42004-022-00655-x
• Publication Date: 2022-03-17T11:04:45Z
• Authors: Feng-Wei Guo; Xiao-Feng Mou; Yong Qu; Mei-Yan Wei; Guang-Ying Chen; Chang-Yun Wang; Yu-Cheng Gu; Chang-Lun Shao
• Keywords: Aldol reaction; Tetrahydrofuran

The strong antibacterial, antiviral and anticancer activities demonstrated by quinolones make them promising lead structures important synthetic targets for drug discovery. Here, we report, to the best of our knowledge, first scalable total synthesis (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton. This strategy explores E-stereoselective Horner-Wadsworth-Emmons (HWE) olefination as key step assemble isopropenyl substituted tetrahydrofuran onto core, which is built highly diastereoselective intramolecular aldol reaction. Moreover, two sets stereoisomers aniduquinolone A with substantially overlapping NMR data were synthesized completely assigned unambiguously comprehensive analysis both their spectroscopic X-ray diffraction data. Unexpectedly, aflaquinolones C, D that feature different 2,4-dimethyl cyclohexanone moieties transformed successfully from treating TFA. methodology delineated herein can be applied broadly natural alkaloids containing core structure 5-hydroxy-4-aryl-quinolin-2(1H)-one.