Synthesis of Caprazamycin Analogues and Their Structure-Activity Relationship for Antibacterial Activity

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• 作者：Shinpei Hirano ; Satoshi Ichikawa ; Akira Matsuda
• 刊名：Journal of Organic Chemistry
• 出版年：2008
• 出版时间：January 18, 2008
• 年：2008
• 卷：73
• 期：2
• 页码：569 - 577
• 全文大小：223K
• 年卷期：v.73,no.2(January 18, 2008)
• ISSN：1520-6904

文摘

Synthesis of palmitoyl caprazol 7, which possesses a simple fatty acyl side chain at the 3' ''-position ofthe diazepanone moiety, was carried out and their antibacterial activity was evaluated. The key elementsof our approach include the improved synthesis of the key 5'--O-aminoribosyl-glycyluridine derivative,installation of the palmitoyl side chain to the cyclization precursor, and the construction of the diazepanoneby an intramolecular reductive amination. The second generation synthesis of (+)-caprazol was alsoestablished. Palmitoyl caprazol 7 exhibited antibacterial activity against Mycobacterium smegmatisATCC607 (MIC = 6.25 g/mL) with potency similar to that of the caprazamycins (CPZs). Palmitoylcaprazol 7 and N^6'-desmethyl palmitoyl caprazol 28 also exhibited antibacterial activity against drug-resistant bacteria including methyciline-resistant Staphylococcus aureus (MRSA) and vancomycin-resistantEnterococcus (VRE) strains (MIC = 3.13-12.5 g/mL).