Total Syntheses and Antibacterial Evaluations of Neocyclomorusin and Related Flavones

Abstract

Neocyclomorusin (1), a natural bioactive pyranoflavone mainly isolated from plants of the Moraceae family, was synthesized for the first time using a Friedel–Crafts reaction, a Baker–Venkataraman (BK-VK) rearrangement, a selective epoxidation, and a novel SN2-type cyclization as the key steps. The present protocol was also successfully applied for the total synthesis of oxyisocyclointegrin (2). Structurally related natural products morusin (23) and cudraflavone B (24) were also prepared. We investigated the antibacterial activities of these natural compounds against both Gram-negative and Gram-positive strains. The prenylated flavones, morusin (23) and cudraflavone B (24), showed comparable activity to ampicillin and kanacycin A against Staphylococcus aureus. Both morusin (23) and cudraflavone B (24) showed better antibacterial activities than ampicillin against the Gram-positive bacteria Staphylococcus epidermidis and Bacillus subtilis. Both neocyclomorusin (1) and oxyisocyclointegrin (2) displayed disappointing antimicrobial activities against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus subtilis strains.

Total Synthesis of Kuwanons A and B and Discovery of Their Antibacterial Mechanism

“…17 After that, the C-2 phenol of 8 was protected by a benzyl group (−Bn) to afford compound 9, which was hydrolyzed to obtain key intermediate 10 in 95% yield. 18 Once the desired 10 was in hand, it was necessary to synthesize the requisite MOM-protected acetophenone 11 for the desired esterification. Therefore, we protected 2,4dihydroxyacetophenone ( 4 methoxymethyl bromide (MOMBr) and N,N-diisopropylethylamine (DIPEA) to afford 11 in 96% yield on a multigram scale.…”

“…We attributed our failure to the instabilities of the MOM groups and the isopentenyl group in those strongly acidic conditions; thus compound 15 was stirred in a weak acid media (AcONa/AcOH) at 100 °C to give the cyclic product 16 successfully. [18][19][20]27 It should be noted that the C-5 MOM was simultaneously removed during the cyclization process.…”

Perplexing Polyphenolics: The Isolations, Syntheses, Reappraisals, and Bioactivities of Flavonoids, Isoflavonoids, and Neoflavonoids from 2016 to 2022

“…Their 60% KOH solution treatment afforded compounds 276 and 277 , respectively. Finally, the selective epoxidation of compound 274 by m CPBA in the presence of K 2 CO 3 at 0–5 °C and subsequent hydrolysis using KOH produced morusin ( 276 ) with a yield of 45% over two steps [ 80 ].…”

“…However, they were inactive against E.coli, and only compounds 276 and 277 exhibited potent antibacterial activity against the other bacteria. As the active compounds contained an isopentane group at C3, and a pyran ring fused to the A ring (motifs absent in compounds 264 and 278 ), the substitutions are likely activating groups [ 80 ].…”

Synthesis of Mono- and Polyazole Hybrids Based on Polyfluoroflavones

“…Flavones based on a 2-phenylchromen-4-one backbone are important heteroaromatic scaffolds in organic chemistry due to their availability and significant synthetic and biological potential [ 1 , 2 , 3 , 4 , 5 ]. The uniqueness of this heterocyclic backbone is also due to the fact that its derivatives are widely represented in the plant world, which often determines their diverse biological action [ 6 , 7 , 8 , 9 , 10 , 11 ]. Isolation, identification, and chemical modification of flavones of plant origin is one of the rapidly developing areas in drug design [ 12 , 13 ].…”