The synthesis and antibacterial activity of totarol derivatives. Part 2: Modifications at C-12 and O-13
The synthesis and antibacterial activity of totarol derivatives. Part 2: Modifications at C-12 and O-13
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DOI：
10.1016/s0968-0896(00)00095-x
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发表时间：
2000-07-01
影响因子：
3.5
通讯作者：
Furneaux, RH
中科院分区：
文献类型：
--
作者：
Evans, GB;Furneaux, RH
甲硫醇(1)的C-12和C-13芳环取代基的改变得到了系列的衍生物2-14，C-12上的取代基只得到了2a-14a。这些类似物中的大多数在体外对下列细菌进行了抗菌试验：β-内酰胺酶阳性和高水平庆大霉素耐药粪肠球菌、青霉素耐药肺炎链球菌、甲氧西林耐药金黄色葡萄球菌(MRSA)和多重耐药肺炎克雷伯菌。根据构效关系对结果进行了评价，结果表明：(A)总的来说，C-13位的酚类部分对抗革兰氏阳性菌的抗菌活性是必不可少的；(B)C-12位的衍生化对这类化合物的抗菌活性有不良影响，而(C)所有被测试的化合物对革兰氏阴性肺炎克雷伯氏菌都没有效果。(C)2000爱思唯尔科学有限公司。保留所有权利。
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: beta-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 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 compounds, while (c) all compounds tested are ineffective against the Gram-negative Klebsiella pneumoniae. (C) 2000 Elsevier Science Ltd. All rights reserved.