Synthesis of prenylated benzaldehydes and their use in the synthesis of analogues of licochalcone A.
In this paper, a general applicable synthesis of prenylated aromatic compounds exemplified by prenylated benzaldehydes starting from readily available acetophenones is described. The synthesized benzaldehydes are used to prepare a number of novel analogues of Licochalcone A, a known antibacterial compound, and for the exploration of the pharmacophoric elements that are essential for the antibacterial activity. It is shown that the hydroxyl group in the A ring is essential for the activity and that the hydroxyl group in the B ring has no influence on the antibacterial effect of Licochalcone A. Furthermore, it is shown that the prenyl group at the position 5 of the B ring also has a dominating influence on the activity. This aliphatic group can be replaced by other lipophilic long chained substituents in order to maintain the activity.
Kromann
Hasse
H
Lica Pharmaceuticals A/S, Symbion Science Park, Fruebjergvej 3, DK-2100 Copenhagen, Denmark.
Larsen
Mogens
M
Boesen
Thomas
T
Schønning
Kristian
K
Nielsen
Simon Feldbaek
SF
D000098:Acetophenones / Q000737:chemistry / Q000378:metabolism; D001547:Benzaldehydes / Q000138:chemical synthesis* / Q000494:pharmacology; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D047188:Chalcones; D008826:Microbial Sensitivity Tests; D009387:Neoprene / Q000737:chemistry*; D017368:Protein Prenylation; D013211:Staphylococcus aureus / Q000187:drug effects*
D000098:Acetophenones; D001547:Benzaldehydes; D047188:Chalcones; C016077:prenyl; D002599:Chalcone; D009387:Neoprene; C070840:licochalcone A