Wang Li-Sheng, Xiang Jia-Chen, Wu An-Xin
State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.
School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, P. R. China.
Chem Commun (Camb). 2024 Nov 1;60(88):12803-12815. doi: 10.1039/d4cc04288c.
Natural product total synthesis has trailblazed in the era of multistep synthesis. The strategic application of existing synthetic methodologies and the stepwise construction that revolves around newly developed, tailored key steps, are two basic tactics in the principle of classic retrosynthetic analysis. However, a new synthetic model, termed self-organized total synthesis, has emerged in recent years, enabling the rapid creation of specific natural products by a one-pot reaction. Distinct from conventional analysis associated with certain bond disconnections, the design of self-organized total synthesis focuses on seeking a series of self-organized reaction sequences which can be integrated compatibly under a uniform condition, therefore allowing the entire sequence to proceed in one pot, and most importantly, starting from commercially available feedstocks or biomass materials. Whilst dauntingly challenging, this synthetic strategy is more consistent with the biogenetic pathway of natural products compared with conventional counterparts, and will hopefully provide the shortest synthesis for such natural products. Through this rational analysis, one-pot total synthesis is no longer in the way of serendipity but can be precisely designed and manipulated. In this review, we account for the definition, delimitation, and categorization of self-organized total synthesis and then elucidate a comprehensive understanding of this synthetic strategy based on our intensive explorations. We also highlight the contributions of other research groups in this growing field and anticipate that it will give rise to advancing new methodologies, as well as new concepts within organic synthesis.
天然产物全合成在多步合成时代起到了开拓作用。现有合成方法的策略性应用以及围绕新开发的、量身定制的关键步骤进行逐步构建，是经典逆合成分析原理中的两种基本策略。然而，近年来出现了一种新的合成模式，即自组装全合成，它能够通过一锅法反应快速合成特定的天然产物。与传统的基于某些键断裂的分析不同，自组装全合成的设计侧重于寻找一系列能够在统一条件下兼容整合的自组装反应序列，从而使整个序列能够在一锅中进行，并且最重要的是，从市售原料或生物质材料开始。尽管这项合成策略极具挑战性，但与传统方法相比，它与天然产物的生物合成途径更为契合，有望为这类天然产物提供最短的合成路线。通过这种合理分析，一锅法全合成不再依赖偶然发现，而是可以精确设计和操控。在这篇综述中，我们阐述了自组装全合成的定义、界定和分类，然后基于我们的深入探索阐明对这种合成策略的全面理解。我们还强调了其他研究团队在这个不断发展的领域所做出的贡献，并预计它将推动新方法以及有机合成新观念的发展。
