The synthesis and antibacterial activity of totarol derivatives. Part 2: Modifications at C-12 and O-13

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 a t C-12 gave exclusively 2a-14a. The majority of these analogues were tested in vitro against the following organisms: beta-lactamase-positive and high level gentamycin-resistant Enterococcus faecalis, penicillin-resistant Str eptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and multiresistant Klebsiella pneumoniae. The results were evaluated in ter ms of structure-activity relationship which reveals that: (a) the phenolic moiety at C-13, in general, is essential for antibacterial activity at < 32 mu g/mL against Gram-positive species, and (b) derivatization at C-12 has an undesirable effect on the antibacterial activity of this class of compou nds, while (c) all compounds tested are ineffective against the Gram-negati ve Klebsiella pneumoniae. (C) 2000 Elsevier Science Ltd. All rights reserve d.