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    • 85. 发明公开
    • Methods of preparing substituted tetracyclines with transition metal-based chemistries
    • 一种制备取代的四环素与过渡金属类的化学过程
    • EP2327686A3
    • 2012-08-22
    • EP10182808.5
    • 2000-09-13
    • TRUSTEES OF TUFTS COLLEGE
    • Nelson, Mark, L.Rennie, GlenKoza, Darrell
    • C07C237/26C07C231/12A61K31/65A61P31/04
    • C07C237/26C07C231/12C07C2603/46
    • The present invention relates to novel chemistries which allow for heretofore unobtainable substituted tetracycline compounds which exhibit significant antibacterial activity. The methods disclosed herein utilize reactive tetracycline-based precursor compounds, reactive organic substituent precursors and transition metal catalysts under conditions such that a tetracycline compound substituted with the desired organic substituent is formed. In one embodiment of the invention, a substituted tetracycline compound may be prepared by combining a reactive tetracycline-based precursor compound such as an arene tetracycline diazonium salt, and a reactive organic substituent precursor, e.g., alkenes, substituted alkenes, vinyl monomers, aromatics and heteroaromatics, in the presence of a transition metal catalyst, such as palladium chloride, under conditions such that a tetracycline compound substituted with the organic substituent is formed. Such compounds may optionally act as intermediates for making other compounds, e.g., hydrogenation of unsaturated groups on the substituent.
    • 本发明涉及新的化学物质,其允许表现出显著抗菌活性迄今无法得到的substituiertem四环素化合物。 在游离缺失利用检查条件下反应性四环素的前体化合物,反应性有机取代基前体和过渡金属催化剂的方法中盘做了与所期望的有机取代基四环素化合物substituiertem形成。 在本发明的一个实施例,substituiertem四环素化合物可以通过组合反应性四环素的前体化合物来制备:如芳烃四环素重氮盐,和反应性有机取代基前体,例如,烯烃,substituiertem烯烃,乙烯基单体,芳族化合物和 杂芳族化合物,在过渡金属催化剂的存在下:测试如氯化钯,的条件下做了四环素化合物substituiertem与有机取代基形成。 搜索化合物可任选用作中间体用于制备其它化合物,E. G.,上的取代基不饱和基团的氢化。