Łysakowska Magdalena, Balzarini Jan, Piotrowska Dorota G
Faculty of Pharmacy, Bioorganic Chemistry Laboratory, Medical University of Łódź, Łódź, Poland.
Arch Pharm (Weinheim). 2014 May;347(5):341-53. doi: 10.1002/ardp.201300382. Epub 2014 Feb 17.
Moderate diastereoselectivities (d.e. 2-62%) of isoxazolidine homonucleotides were observed for cycloadditions between N-methyl-C-(diethoxyphosphoryl)nitrone and N-allyl nucleobases, with trans-isoxazolidines predominating. The stereochemistry of the substituted isoxazolidines was established based on 2D NOE experiments performed for uracil-containing cycloadducts. The cis- and trans-isoxazolidine phosphonates obtained herein were evaluated in vitro for activity against a broad range of DNA and RNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations, but some of them were found to inhibit the proliferation of L1210 cells with IC50 values in the range of 33-100 µM.
对于N-甲基-C-（二乙氧基磷酰基）硝酮与N-烯丙基核碱基之间的环加成反应，异恶唑烷同核苷酸表现出中等的非对映选择性（d.e. 2-62%），反式异恶唑烷占主导。基于对含尿嘧啶环加成产物进行的二维NOE实验确定了取代异恶唑烷的立体化学。本文获得的顺式和反式异恶唑烷膦酸酯在体外针对多种DNA和RNA病毒的活性进行了评估。在亚毒性浓度下，没有一种化合物具有抗病毒活性，但发现其中一些化合物能够抑制L1210细胞的增殖，IC50值在33-100 μM范围内。
