Preparation of enantioenriched quaternary centers and synthesis of complex alkaloids - Préparation de carbones quaternaires énantioenrichis et synthèse d'alcaloides complexes

对映体富集的四元中心的制备和复杂生物碱的合成 - Preparation de Carbones quaternaires énantioenrichis et Synsè dalcaloides Complexes

• 批准号: 249564-2012
• 负责人: Bélanger, Guillaume
• 金额: $ 3.28万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=524704
• 关键词: Preparation; enantioenriched; quaternary; centers; synthesis

Classical syntheses of polycyclic alkaloids are often long and involve a large number of steps principally due to a sequential preparation of every cycle of the molecule. It is well established that one-pot multi-reactions (reaction cascades and reaction sequences) provide undeniable advantages over stepwise processes, such as economy of time, resource management, labor, and waste generation. In this vein, we will use a sequence Vilsmeier-Haack cyclization and azomethine ylide cycloaddition (V-H/3+2) that we developed recently to create 3 C-C bonds and 3 cycles in a single transformation, and use this strategy to synthesize daphnilactone B-type and yuzurimine-type alkaloids (never synthesized before), as well as Aspidosperma and Strychnos alkaloids (in 33 to 40% less steps than published non racemic syntheses). With such a rapid approach, many members of these families will be readily accessible, which will undoubtedly catch the attention of several synthetic chemists for the design, and of medicinal chemists for using these cores in drug development.

多环生物碱的经典合成通常很长，并且主要由于分子的每个环的顺序制备而涉及大量步骤。众所周知，一锅多反应（反应级联和反应顺序）提供了优于分步方法的不可否认的优点，例如节省时间、资源管理、劳动力和废物产生。在这方面，我们将使用我们最近开发的序列Vilsmeier-Haack环合和甲亚胺叶立德环加成（V-H/3+2），在一次转化中产生3个C-C键和3个环，并使用该策略合成瑞香内酯B型和尤珠利明型生物碱（以前从未合成过），以及Aspidosperma和Strychnos生物碱（比公开的非外消旋合成少33 - 40%的步骤）。有了这样一种快速的方法，这些家族的许多成员将很容易获得，这无疑将引起几位合成化学家的注意，用于设计，以及药物化学家在药物开发中使用这些核心。