自然界中种类丰富、骨架多样、作用机制各异的活性天然产物是新药研发的重要源头，然而许多天然来源的有效成分存在含量低、纯化工艺复杂、难以大量获得的问题，成为靶标确证及成药性研究的重要障碍。因此，天然产物合成成为高效、大量、靶向获得活性成分的重要手段。吲哚生物碱类天然产物具有结构复杂、生物活性优良等特点，是药物发现的重要来源之一。色胺炔酰胺作为理想的合成砌块，可以简洁高效地构建各种吲哚生物碱母核，进而合成相关天然产物。富电炔酰胺的碳碳三键可被酸、金、银、铜等催化剂活化，从而被吲哚C-3位进攻发生环化反应。色胺炔酰胺环化过程的进攻方式一般分为2类：一种是电性效应主导的进攻α位的类型，另一种是以配位效应主导的进攻β位的类型。色胺炔酰胺发生环化后级联分子内捕获、分子间捕获以及重排等过程，可以快速构建出四环吲哚、β-咔啉吲哚、螺环吲哚和氮杂䓬并吲哚等重要的吲哚生物碱核心骨架。详细介绍了基于色胺炔酰胺高效合成吲哚生物碱的天然产物合成策略，并总结其一般反应活性规律和特点，为吲哚生物碱类天然产物的合成、开发和利用提供参考。

The bioactive natural products with rich species, diverse skeletons and different action mechanisms in nature are an important source of new drug research and development. However, many active components from natural products have the problems of low content, complex extraction process and difficult to obtain in large quantities, which have become an important obstacle to target confirmation and druggability. Therefore, the synthesis of natural products has become an important means to obtain active components with high efficiency, large amount and targeting. Indole alkaloid natural products are one of the important sources of drug discovery due to their complex structures and excellent biological activities. Tryptamine-ynamide, as an ideal synthetic building block, can be used to construct various skeletons of indole alkaloids concisely and efficiently, and synthesize related natural products. The C-C triple bond of the electron-rich ynamide could be activated by acid, gold, silver, copper and other catalysts, which then could be attacked by C-3 position of indole to form cyclic structures. The attack modes of tryptamine-ynamides cyclization process are generally divided into two categories including α type attack dominated by electronic effect and β type attack dominated by coordination effect. After the cyclization of tryptamine-ynamides, the processes of intramolecular capture, intermolecular capture and rearrangement could be cascaded, which can be quickly used to construct tetracyclic indoles, β-carboline indole, spiro indole, azacycloindole and other important core skeletons of indole alkaloids. Therefore, the synthetic strategies of natural products for the efficient synthesis of indole alkaloids based on tryptamine-ynamide were introduced in detail in this paper, and the general reaction activity rules and characteristics were summarized to provide reference for the synthesis, development and utilization of indole alkaloid natural products.

R284.3

辽宁省“兴辽英才计划”青年拔尖人才（XLYC807091）