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化学学报
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化学学报 ›› 2002, Vol. 60 ›› Issue (10): 1887-1892. 上一篇    下一篇

研究论文

2',3'-双脱氢-2',3'-双脱氧胸苷(d4T)5'-硫代磷酰氨基酸酯的合成和谱学分析

苗志伟;冯玉萍;付华;涂光忠;赵玉芬   

  1. 清华大学化学系.北京(100084);北京微量化学研究所.北京(100091)
  • 发布日期:2002-10-15

Synthesis and Spectroscopic Analysis of 2',3'-Didehydro-2',3'- dideoxythymidine (d4T)5'-thiophosphoramidates

Miao Zhiwei;Feng Yuping;Fu Hua;Tu Guangzhong;Zhao Yufen   

  1. The Key Laboratory of Bioorganic Phosphorus Chemistry, Ministry of Education, Department of Chemistry, School of Life Sciences and Engineering, Tsinghua University.Beijing(100084);Beijing Institute of Microchemistry.Beijing(100091)
  • Published:2002-10-15

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379

被引次数

3

HIV逆转录酶是治疗艾滋病的有效靶点，核苷-磷酰氨基酸酯是HIV逆转录酶的 有效抑制剂，但是这类化合物容易在体内被核酸酶水解。本研究设计合成了对核酸 酶具有抵抗作用的2',3'-双脱氢-2',3'-双脱氧胸苷5'-硫代磷酰氨基酸酯化合物， 这类化合物可以有效地透过细胞膜经过细胞激酶的作用，进入HIV逆转录酶的作用 位点，病毒实验表明该类化合物对MT-4细胞具有较好的抗HIV病毒活性。报道了2', 3'-双脱氢-2',3'-双脱氧胸苷5'-硫代磷酰氨基酸酯化合物的合成，及利用NMR， IR和ESI-MS谱进行的结构表征和构象分析。

关键词: 硫代磷酰, 胸腺, 结构表征, 构象, 核磁共振谱法, 红外分光光度法, 质谱法, 艾滋病

Nucleoside reverse transcriptase inhibitors are the only drugs so far approved for the treatment of AIDS. Nucleoside 5'- phosphorothioates is relatively resistant to enzymatic transformations. Novel 2',3'-didehydro-2',3'-dideoxythymidine (d4T) 5'- thiophosphoramidates have been prepared by thiophosphorochloridate chemistry. These materials were designed to act as membane-soluble prodrugs of the bioactive free nucleotides. In vitro evaluation reveals that the compounds have a pronounced, selective anti-HIV activity in MT-4 cells. The new compounds are characterized by NMR, IR and ESI-MS. The results from NMR experiments indicate that there are anti-orientation for glycosyl grouping in compounds 5a～5e.

Key words: THIOPHOSPHORYL, THYMUS GLAND, STRUCTURE CHARACTERISTICS, CONFORMATION, NMR, IR, MS, AIDS

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