6-Hydroxy to 6-amino tethered ring-to-ring macrocyclic aminoglycosides as probes for APH(3′)-IIIa kinase

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• 作者：Stephen Hanessian ; Janek Szychowski ; Natalhie B. Campos-Reales Pineda ; Alex ; ra Furtos ; Jeffrey W. Keillor
• 关键词：Aminoglycosides ; Phosphotransferase ; APH(3′ ; )-IIIa kinase ; Paromomycin
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 出版时间：1 June 2007
• 年：2007
• 卷：17
• 期：11
• 页码：3221-3225
• 全文大小：364 K

文摘

Based on molecular modeling and available X-ray structure data on aminoglycosides complexed with a bacterial ribosomal surrogate or with a kinase, two analogues of paromomycin were prepared by tethering the 6-OH and the 6-NHb>2b> group with a five-carbon bridge. Only one of two possible hydroxyl groups was phosphorylated by the kinase. The application of ring closure metathesis is presented for the first time to construct bridged macrocyclic analogues in the aminoglycoside series.