Nine-membered N-heterocycle scaffolds are widely found in natural products and biologically active molecules. The rigid structure of the medium-sized ring plays important roles in the regulation of their biological and pharmacological activities. Therefore, nine-membered N-heterocycle is one of the most attractive medium-sized ring compounds. Because of the increasing entropy and ring extension of nine-membered ring skeleton, the synthesis of nine-membered N-heterocycles is still difficult; especially the effective control of substituent stereoselectivity for the nine-membered ring is one of the greatest challenging topics This review summarizes the novel synthetic strategies of nine-membered N-heterocycles and their applications in the synthesis of natural products and pharmaceutically active molecules containing nine-membered ring scaffold in recent years. Keywords nine-membered N-heterocycles; medium-sized ring compounds; cyclization; cycloaddition; ring expansion 氮杂环结构广泛存在天然产物和药物分子中, 是新 药设计和分子药理活性研究中的优势骨架 [1] . 中环骨架 (8~12 元环)的氮杂环化合物在自然界中广泛存在, 由 于环张力和熵增不利的影响, 中环骨架化合物的构建一 直是有机合成中极富挑战的难点之一 [2] . 其中, 九元氮 杂环化合物是最被关注的中环化合物之一 [3] . 如生物碱 antaroide [4] , (±)-cleavamine [5] , melohenine B [6] , (+)-lycoposerramine B [7] , (-)-rhazinilam [8] , palhinine A [9] 等(图 1).