Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA.
J Am Chem Soc. 2009 Dec 2;131(47):17087-9. doi: 10.1021/ja907924j.
Laulimalide is a structurally unique 20-membered marine macrolide displaying microtubule stabilizing activity similar to that of paclitaxel and the epothilones. The use of atom-economical transformations such as a Rh-catalyzed cycloisomerization to form the endocyclic dihydropyran, a dinuclear Zn-catalyzed asymmetric glycolate aldol reaction to prepare the syn 1,2-diol, and an intramolecular Ru-catalyzed alkene-alkyne coupling to build the macrocycle enabled us to synthesize laulimalide via an efficient and convergent pathway. The designed synthetic route also allowed us to prepare an analogue of the natural product that possesses significant cytotoxic activity.
拉罗肽是一种结构独特的 20 元海洋大环内酯,具有与紫杉醇和埃坡霉素类似的微管稳定活性。使用原子经济性转化,如 Rh 催化的环化异构化形成内环二氢吡喃、双核 Zn 催化的不对称甘油酸酯醛缩合反应制备顺式 1,2-二醇以及分子内 Ru 催化的烯炔偶联反应构建大环,使我们能够通过高效和收敛的途径合成拉罗肽。设计的合成路线还使我们能够制备具有显著细胞毒性活性的天然产物类似物。