Total synthesis of marine natural products without using protecting groups

摘要

全合成(用结构较简单的起始材料来合成复杂有机分子的过程)在过去 50年里取得了引人瞩目的进步。尽管取得了这些进步，但能够生成足 够数量大天然产物、供进一步研究的合成路径仍然是一个相当大的挑 战。为了满足这一需求，一组化学家发现，在合成过程中使用“保护” 官能团的例行做法是实现这一目标的一个关键障碍。在一个分子的其 他部分在发生化学转变的时候，经常需要“保护”官能团来掩蔽该分 子的活性部分。为了演示新方法所具有的潜力，该文作者们在没有使 用任何一个“保护”官能团的情况下合成了一个大家族的海洋生物碱 中的几个成员。该方法使他们能够在lO步或更少的反应步骤中获得以 前需要20步或更多化学反应步骤才能获得的数量有意义的分子。%The field of organic synthesis has made phenomenal advances in the past fifty years, yet chemists still struggle to design synthetic routes that will enable them to obtain sufficient quantities of complex molecules for biological and medical studies. Total synthesis is therefore increasingly focused on preparing natural products in the most efficient manner possible. Here we describe the preparative-scale, enantioselective, total syntheses of members of the hapalindole, fischerindole, welwitindolinone and ambiguine families, each constructed without the need for protecting groups—the use of such groups adds considerably to the cost and complexity of syntheses. As a consequence, molecules that have previously required twenty or more steps to synthesize racemically in milligram amounts can now be obtained as single enantiomers in significant quantities in ten steps or less. Through the extension of the general principles demonstrated here, it should be possible to access other complex molecular architectures without using protecting groups.