药物成瘾和药物滥用严重损害人类健康并威胁社会公共安全，但在临床上仍缺乏可靠的治疗手段和药物，亟待研发新型高效的治疗药物。Ibogaine作为具有良好的抗成瘾活性的分子实体，对其进行结构改造和构效关系研究已成为该领域的研究热点。该类生物碱含有一个C3-取代的吖庚环并[4,5-b]吲哚核心骨架，其合成方法的研究可为相关类似物的合成提供可靠策略，对推动抗成瘾药物的发展具有重要意义。目前已有多种合成方法，但不对称合成策略的发展还十分有限。本项目以基于优势骨架导向的多样性合成(pDOS)理念为指导，选取iboga alkaloids三环骨架为优势骨架，拟从简单的色胺衍生物出发，通过不对称酸催化分子内Michael加成/重排/芳构化串联反应立体选择性地构建目标结构，并探索该方法在构建小分子库和伊博格生物碱的全合成中的应用，为构建高质量的小分子库和进行抗成瘾活性分子实体的筛选提供可靠策略。

Drug addiction and abuse have attracted great attention globally, not only because they damage drug addicts’ health, but also because they threaten public safety. Most addiction is so far without any reliable treatment, so it’s demanding to develop new anti-addiction drug. Ibogaine possesses good anti-addictive effects. The study of its structural modification and structure-activity-relationship have become a hot area of research in this field. Iboga alkaloids share a C3-substituted azepino[4,5-b]indole skeleton, the synthetic approach development of which can support the syntheses of its derivatives and accelerate the study of anti-addiction drug. So far, a number of methods have been developed, but few of them are enantioselective..In this proposal, based on the concept of privileged-substructure-based diversity-oriented synthesis (pDOS), an enantioselective Brønsted acid-catalyzed Michael/rearrangement/rearomatization cascade of easily attainable tryptamine derivatives is designed to synthesize C3-substituted azepino[4,5-b]indoles and applied to synthesize iboga alkaloids and construct a molecular library of high quality, laying solid foundation for further screening of lead compounds.