【作者】 陈伟；

【导师】 陈洪斌；

【作者基本信息】 厦门大学 ， 物理化学， 2018， 硕士

【摘要】 催化不对称Henry反应是一类非常重要的立体选择性碳-碳键生成反应,其产物手性β-硝基醇可以转化为多种重要的手性中间体,从而为诸多手性分子、砌块的不对称合成提供了便捷的途径,因而其在手性天然产物和药物的合成中具有重要的应用。虽然已被广泛的研究,但已有的不对称Henry反应催化剂体系大都存在催化剂昂贵、投入量大、反应条件严苛、底物通用性差等不足。而手性氨基醇具有来源丰富、制备简单、与金属离子有良好的配位能力及配位形式多样等优点,在不对称催化中具有重要的用途。我们实验室在前期的工作中发现,手性氨基醇-Cu(Ⅱ)催化体系能够有效地催化羰基底物的不对称Henry反应。本论文的主要目的在于进一步拓展该手性氨基醇-Cu(Ⅱ)催化体系在不对称Henry反应中的应用,并利用该反应为关键步骤,探索更多高效便捷合成手性天然产物和药物分子的方法。本论文主要包括以下两部分内容:1.催化不对称Henry反应合成手性苯并呋喃-β-氨基醇以手性氨基醇-Cu(Ⅱ)络合物为催化剂,催化苯并呋喃-2-甲醛类化合物与硝基甲烷的不对称Henry反应,得到具有高对映选择性的苯并呋喃-β-硝基醇中间物,并经过“一锅法”转化得到具有重要生物、药物活性(如β-受体阻滞剂)的手性苯并呋喃-β-氨基醇类化合物。2.催化不对称Henry反应合成(-)-Spirbrassinin及其衍生物的研究以手性氨基醇-Cu(Ⅱ)络合物为催化剂,催化Isatin与硝基甲烷不对称Henry反应,并将Henry反应产物进一步转化为具有抗真菌、抗癌活性的植物抗毒素(-)-spirbrassinin及其类似物。从而为后续的生物活性研究打下了坚实的合成基础。更多还原

【Abstract】 The catalytic asymmetric Henry reaction has been a hot research topic since its first report in 1990s.Besides as a classical carbon-carbon bond-formation method,catalytic asymmetric Henry reaction can enantioselectively accomplish the Carbon chain growth.And the Henry product,chiral P-nitro alcohols,can be conveniently converted into many functional groups via simple transformation.Therefore,it give us an easy and efficient method to synthesize many chiral molecules and blocks,which play an important role in development of chiral natural products and drugs.Many catalytic systems have been developed in the last few decades,however,most of them share some disadvantages such as expensive catalysts with high loadings,harsh reaction conditions,and poor generality of substrate.Chiral amino alcohols are widely applied in asymmetric catalysis because of their advantages such as abundant sources,easy preparation,excellent coordination ability and versatile coordination modes with transition metals.Previously our lab have developed new chiral amino alcohol-copper(II)complexes as efficient catalyst for asymmetric Henry reaction.The purpose of this dissertation is to further exploit the application of our chiral amino alcohol-copper(II)catalytic system in Henry reaction,as well as their further utilization in the efficient synthesis of chiral natural products and drugs.This dissertation mainly includes the following two parts:1.Efficient synthesis of chiral benzofuryl β-amino alcohols via a catalytic asymmetric Henry reactionThe catalytic asymmetric Henry reaction of benzofuran-2-carbaldehydes with nitromethane were carried out in the presence of chiral amino alcohol-copper(II)complex as the catalyst.All the substrates stested herein gave their corresponding Henry adducts(benzofuran-2-nitroethanols)with moderate to good isolated yields with good to excellent ee values.Using this reaction,structurally-diverse benzofurylβ-amino alcohols with impressive physiological and drug activities such asβ-adrenergic blocking activities could be conveniently prepared in a one-pot transformation from the Henry adducts.2.Efficient synthesis of(-)-spirbrassinin and analogue via a catalytic asymmetric Henry reactionIn the presence of chiral amino alcohol-copper(II)complex,various isatins reacted well with nitromethane,which gave good isolated yields and medium enantioselectivity.Further transformation of the isatin-nitromethane Henry adducts in short steps afforded a kind of phytoalexins(-)-spirbrassinin and its analogues,which displays various biological properties such as antifungal and antitumor.We wish this work may facilitate the biological activity studies in the near future.更多还原