The synthesis and antibacterial activity of totarol derivatives. part 2: modifications at C-12 and O-13 Original Research Article

Alterations of the C-12 and C-13 aromatic ring substituents of totarol (1) afforded the series of derivatives 2–14, and introduction of substituents at C-12 gave exclusively 2a–14a. The majority of these analogues were tested in vitro against the following organisms: β-lactamase-positive and high level gentamycin-resistant Enterococcus faecalis, penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and multiresistant Klebsiella pneumoniae. The results were evaluated in terms of structure–activity relationship which reveals that: (a) the phenolic moiety at C-13, in general, is essential for antibacterial activity at <32 μg/mL against Gram-positive species, and (b) derivatization at C-12 has an undesirable effect on the antibacterial activity of this class of compounds, while (c) all compounds tested are ineffective against the Gram-negative Klebsiella pneumoniae.