Synthesis of variously oxidized abietane diterpenes and their antibacterial activities against MRSA and VRE.
Variously oxidized 12 natural abietanes, 6,7-dehydroferruginol methyl ether (3), ferruginol (5), 11-hydroxy-12-oxo-7,9(11),13-abietatriene (7), royleanone (9), demethyl cryptojaponol (12), salvinolone (14), sugiol methyl ether (16), sugiol (17), 5,6-dehydrosugiol methyl ether (19), 5,6-dehydrosugiol (20), 6beta-hydroxyferruginol (23), and taxodione (25) were synthesized. Antimicrobial activities of synthesized phenolic diterpenes and their related compounds against MRSA and VRE were evaluated. Phenols (12-hydroxyabieta-8,11,13-trien-6-one 22 and 23), catechols (12 and 14) and taxodione 25 showed potent activity with 4-10 microg/mL of MIC against MRSA and 4-16 microg/mL of MIC against VRE. (-)-Ferruginol showed more potent activity than natural type (+)-ferruginol. Quinone methide 7 showed the most potent activity with 0.5-1 microg/mL of MIC against both MRSA and VRE.
Yang
Z
Z
Laboratory of Bioorganic Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Japan.
Kitano
Y
Y
Chiba
K
K
Shibata
N
N
Kurokawa
H
H
Doi
Y
Y
Arakawa
Y
Y
Tada
M
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D004224:Diterpenes / Q000138:chemical synthesis / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D016983:Enterococcus / Q000187:drug effects; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D004224:Diterpenes; D010616:Phenanthrenes