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

Abstract

Kuwanons A (1) and B (2) are two natural prenylated flavones isolated from the root bark of Morus alba L. In this study, the first total syntheses of kuwanons A (1) and B (2) were achieved from a common intermediate with overall yields of 6.6% and 11.6%, respectively. Kuwanon B (2) exhibited antibacterial activity against Gram-positive bacteria and concentration-dependent bactericidal activity against Staphylococcus aureus bacteria. Preliminary mechanism of action studies suggested that this compound killed bacteria rapidly by disrupting bacterial membrane integrity

Total Syntheses and Antibacterial Studies of Natural Isoflavones: Scandenone, Osajin, and 6,8-Diprenylgenistein

“…Finally, 16 could be obtained in a satisfactory isolated yield (72%) using acidic alumina as a catalyst and 1,2-dichloroethane (DCE) as a solvent (entry 5) [31][32][33]. Compound 16 was treated with newly prepared sodium dodecane-1-thiolate in reflux DMF to generate natural product 3 in 78% yield [19]. With the key intermediate 15 in hand, we next investigated the di-prenylation of 15 with 1-bromo-3-methylbut-2-ene (17) or 3-methylbut-2-en-1-ol (18) to get compound 16.…”

“…Finally, 16 could be obtained in a satisfactory isolated yield (72%) using acidic alumina as a catalyst and 1,2-dichloroethane (DCE) as a solvent (entry 5) [31][32][33]. Compound 16 was treated with newly prepared sodium dodecane-1-thiolate in reflux DMF to generate natural product 3 in 78% yield [19]. As shown in Table 2, the synthesis of scandenone (1) and osajin (2) commenced with the stereocontrolled preparations of tetracyclic isoflavens 19 and 20, which possessed a linear or angular pyran attached to the A-ring, respectively.…”

Total Synthesis and Antibacterial Evaluation of Lupinifolin and Its Natural Analogues

“…The total synthesis and synthetic approach to flavanones 1 – 5 have never been reported. In our ongoing effort to discover antibacterial agents from natural flavonoids, − we herein report the first total synthesis of the flavanones 1 – 5 and discuss their antibacterial activities.…”

“…To evaluate the in vitro antibacterial activity of prenylated flavanones 1 – 5 and 27 , MICs against four strains of Gram-positive bacteria ( S. aureus ATCC 29213, E. faecalis ATCC 29212, MRSA21-5, and VRE ATCC 51299) and one strain of Gram-negative bacteria ( E. coli ATCC 25922) were determined by using susceptibility testing according to the guidelines of Clinical and Laboratory Standards Institute (CLSI). , Ampicillin was used as a positive control. As shown in Table , all of the natural compounds, except 2 , exhibited potent antibacterial potency toward Gram-positive bacteria with MIC values of 0.25–4.0 μg/mL.…”

“…In contrast, EthD-III, a red fluorescent nucleic acid stain, can only pass through damaged cell membranes. They are frequently combined to detect cell membrane integrity. , As demonstrated in Figure (B), both the blank control and bacteria treated with 8 × MIC of 27 displayed green fluorescence in the NucGreen channel, while the 27 -treated group produced strong red fluorescence, clearly indicating the disruption of cell membrane integrity.…”