糖胺类似物的合成
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摘要
脲类、硫脲类化合物及其衍生物具有优良的抗菌，抗肿瘤等生理活性，是一种重要的有机合成中间体。异(硫)脲类化合物，除了具有杀菌，除草活性外，还是生命体中一氧化氮合酶(Nitric-oxide synthase)的良好抑制剂，对败血性休克和炎症等疾病起到极好的防治作用，同时也是重要的有机合成中间体。磷酰三胺类化合物具有优良的杀虫，抗病毒作用，其中部分已商品化。我们以糖基异(硫)氰酸酯为中间体，将糖环引入到脲及异(硫)脲类化合物中，得到了糖基脲类化合物及糖基异缩二硫脲类化合物。将糖基异缩二硫脲类化合物进一步氧化关环，得到了糖基环状异硫脲类化合物。通过这些化合物的制备，我们希望能够拓宽(硫)脲及异(硫)脲类化合物的抗菌谱，改善其药理活性，对于农药和医药的开发做出贡献。合成得到的所有化合物均未见文献报道，化合物的结构经元素分析、IR、~1H NMR、MS谱进行确证，部分化合物还经过~(31)P NMR谱确证。
本论文的主要工作为：
1．糖基异氰酸酯未经分离直接与磷酰肼类化合物反应，制备糖基亚脲基磷酰三胺类化合物；
2．糖基异硫氰酸酯与异(硫)脲类化合物反应，高产率制备糖基异缩二硫脲类化合物；
3．用溴氧化糖基异缩二硫脲类化合物，制备3-烷硫(氧)基-5-糖胺基-1，2，4-噻二唑类的环状异硫脲化合物。
Ureas, thioureas and their derivatives have strong antibacterial, antitumor activities. They also play an important role in organic synthesis as intermediates. Isoureas, isothioureas and their derivatives are excellent nitric-oxide synthase inhibitors in life for the treatment of septic shock and related inflammatory disorders, besides acting as insecticide, herbcide. They are also appreciated by synthetic chemists. Phosphorotriamides have strong pesticidal and antiviral action, some of them have become commodities. With glycosyl isocyanates and glycosyl isothiocyanates as intermediates, we put glycosyl into ureas and isoureas to get acetylglycosylureylene phosphoric triamides and glycosyl isothiobiurets. Subsequently, glycosyl isothiobiurets are cyclized by oxidizing agents to glycosyl cyclic isothioureas. From these new compounds, we hope to widen their antibacterial activities and improve their pharmacological action, and also make efforts to explore new medicines and pesticides. All new compounds have no
t been reported. Their structures were confirmed by elemental analysis and IR, 'H NMR, MS spectral data. Some parts of them were confirmed by 31P NMR spectral data. The major work of the thesis:
1. The preparation of acetylglycosylureylene phosphoric triamides by the reaction of phosphorodiamidohydrazides with glycosyl isocyanate which not be isolated;
2. The preparation of glycosyl isothiobiurets in high yield by the reaction of glycosyl isothiocyanates with isoureas or isothioureas;
3. The preparation of 3-alkylthio-5-glycopyranosylamino-l,2,4-thiadiazoles by the oxidizing cyclization of glycosyl isothiobiurets.
本论文的主要工作为：
1．糖基异氰酸酯未经分离直接与磷酰肼类化合物反应，制备糖基亚脲基磷酰三胺类化合物；
2．糖基异硫氰酸酯与异(硫)脲类化合物反应，高产率制备糖基异缩二硫脲类化合物；
3．用溴氧化糖基异缩二硫脲类化合物，制备3-烷硫(氧)基-5-糖胺基-1，2，4-噻二唑类的环状异硫脲化合物。
Ureas, thioureas and their derivatives have strong antibacterial, antitumor activities. They also play an important role in organic synthesis as intermediates. Isoureas, isothioureas and their derivatives are excellent nitric-oxide synthase inhibitors in life for the treatment of septic shock and related inflammatory disorders, besides acting as insecticide, herbcide. They are also appreciated by synthetic chemists. Phosphorotriamides have strong pesticidal and antiviral action, some of them have become commodities. With glycosyl isocyanates and glycosyl isothiocyanates as intermediates, we put glycosyl into ureas and isoureas to get acetylglycosylureylene phosphoric triamides and glycosyl isothiobiurets. Subsequently, glycosyl isothiobiurets are cyclized by oxidizing agents to glycosyl cyclic isothioureas. From these new compounds, we hope to widen their antibacterial activities and improve their pharmacological action, and also make efforts to explore new medicines and pesticides. All new compounds have no
t been reported. Their structures were confirmed by elemental analysis and IR, 'H NMR, MS spectral data. Some parts of them were confirmed by 31P NMR spectral data. The major work of the thesis:
1. The preparation of acetylglycosylureylene phosphoric triamides by the reaction of phosphorodiamidohydrazides with glycosyl isocyanate which not be isolated;
2. The preparation of glycosyl isothiobiurets in high yield by the reaction of glycosyl isothiocyanates with isoureas or isothioureas;
3. The preparation of 3-alkylthio-5-glycopyranosylamino-l,2,4-thiadiazoles by the oxidizing cyclization of glycosyl isothiobiurets.
引文
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7. Richard F. H., Joseph J. K. Carbohydrate-urea-based adhesives: Transient Formation of mono-and di-D-Glucosylurea [J], Carbohydr Res., 1989, 189, 103-112.
8. Fischer E. Synthesis of new glucosides [J], Ber., 1914, 47, 1377-1393.
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10. Lindhort T. K. Kieburg C, Solvent-Free preparation of glycosyl isothiocyanates [J], Synthesis, 1995, 1228-1230.
11．曹玲华，解正峰，周传健，刘育亭．双-(N-糖基硫代氨基脲-2-基)硫代膦芳基酸酯的合成[J]，化学通报，2002，65(7)，W054．
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