Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China.
Nat Prod Rep. 2019 Nov 13;36(11):1546-1575. doi: 10.1039/c8np00094h.
Covering: selected examples in the past three decades (up to 2018) The challenging structures and often potent biological activities of naturally occurring macrocycles have attracted much attention among the synthetic community. In a typical retrosynthetic disconnection, commonly used macrocyclization tactics, including macrolactonization, macrolactamization, ring-closing metathesis, olefination, and metal-mediated cross-coupling reactions, are invariably based on linear substrates in which all of the stereogenic centers have already been set forth. Macrocyclizations with the simultaneous installation of the requisite stereogenic centers can be advantageous with respect to a broader substrate spectrum as well as a usually higher overall synthetic efficiency. However, achieving predictably high levels of stereocontrol remains a formidable challenge. In this review, we discuss representative examples of those "nonclassic" macrocyclization strategies in the context of natural product total synthesis. Different types of macrocycle-forming methods are summarized, with a particular focus on the sense of diastereoinduction imparted through the transition-state macrocyclic ring architecture (≥12-membered) or the catalyst.
过去三十年（截至 2018 年）的精选实例 天然存在的大环的挑战性结构和通常很强的生物活性引起了合成界的广泛关注。在典型的反合成切断中，通常使用的大环化策略，包括大环内酯化、大环内酰胺化、环 closing 复分解、烯烃化和金属介导的交叉偶联反应，都不可避免地基于已经提出了所有立体中心的线性底物。具有同时安装所需立体中心的大环化可以在更广泛的底物谱以及通常更高的整体合成效率方面具有优势。然而，实现可预测的高水平立体控制仍然是一个艰巨的挑战。在这篇综述中，我们讨论了在天然产物全合成背景下那些“非经典”大环化策略的代表性实例。总结了不同类型的大环形成方法，特别关注通过过渡态大环环架构（≥12 元）或催化剂赋予的非对映诱导。
