Arumugam Natarajan, Almansour Abdulrahman I, Kumar Raju Suresh, Rajesh Raju, Periyasami Govindasami, Raghunathan Raghavachary
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Med Chem. 2014;10(7):730-7. doi: 10.2174/1573406410666140226115258.
A series of macrocyclic bis-β-lactams has been synthesized in three good yielding steps using a Staudinger [2+2] cycloaddition reaction of ketene derived from phenoxyacetyl chloride as the key step. The reaction provided a diastereomeric mixture of cis-anti-cis (C2-symmetry) and cis-syn-cis (meso) bis-β-lactam grafted macrocycles which were screened for their in vitro antibacterial and antifungal activities against four human pathogenic bacteria and two pathogenic fungi. Compounds 6a and 6b exhibited antibacterial activity at lower concentration against four bacterial pathogens and compounds 10b and 12a showed antifungal activity against two fungal pathogens when compared to reference control.
通过以苯氧乙酰氯衍生的乙烯酮的施陶丁格[2+2]环加成反应为关键步骤，经三步高收率反应合成了一系列大环双β-内酰胺。该反应得到了顺式-反式-顺式（C2对称）和顺式-顺式-顺式（内消旋）双β-内酰胺接枝大环的非对映异构体混合物，并对其针对四种人类致病细菌和两种致病真菌的体外抗菌和抗真菌活性进行了筛选。与参考对照相比，化合物6a和6b在较低浓度下对四种细菌病原体表现出抗菌活性，化合物10b和12a对两种真菌病原体表现出抗真菌活性。
