Department of Chemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
J Am Chem Soc. 2011 Sep 28;133(38):14968-71. doi: 10.1021/ja207496p. Epub 2011 Sep 6.
The complexity and low tractability of antibiotic macrolides pose serious challenges to addressing the problem of resistance through semi- or total synthesis. Here we describe a new strategy involving the preparation of a complex yet tractable macrocycle and the transformation of this macrocycle into a range of erythronolide congeners. These compounds represent valuable sectors of erythromycinoid structure space and constitute intermediates with the potential to provide further purchase in this space. The routes are short. The erythronolides were prepared in three or fewer steps from the macrocycle, which was prepared in a longest linear sequence of 11 steps.
抗生素类大环内酯类的复杂性和低反应性给通过半合成或全合成来解决耐药性问题带来了严重的挑战。在这里，我们描述了一种新的策略，涉及到复杂但可处理的大环的制备以及将该大环转化为一系列红霉素类似物。这些化合物代表了红霉素结构空间的有价值的部分，并且是具有在该空间中进一步探索潜力的中间体。路线很短。从大环内酯类中通过三到四个步骤即可制备得到赤霉素，而大环内酯类则通过最长的 11 步线性序列制备得到。
