Collective synthesis of natural products by means of organocascade catalysis

摘要

通过将两个在自然界中形成的生物合成原理结rn合起来，David MacM…an及其来自普林斯顿大rn学默克催化研究中心的同事建立了一个用来生rn成一系列不同天然产物的强大策略。第一个是rn“有机级联催化”(orgarlocascade)，即一个rn连续的催化级联代替传统的“停止一进行”rn(stop—go)合成方法。第二个是“集体合成”rn(collective syntrlesis)，即利用一个通用合成rn路径来获得一个共同的分子支架，后者通过适rn当微调会成为合成同一化学家族中其他成员的rn通道。该方法通过六种具有高知名度的生物碱rn的非对称全合成得到了演示，这六种生物碱rn是：马钱子碱(st rychnine)、白坚木碱rn(aspidosperrhidine)、右旋异形蔓长春花胺rn(vincadifformine)、阿枯米辛碱rn(akuammicine)、柯蒲木酮碱(Kopsanone)和rn蕊木宁(kopsinine)。%Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine.