马钱子碱的结构修饰和手性应用

Structural Modifications and Chiral Applications of Brucine

从结构修饰与手性应用的角度,综述了关于马钱子碱的最新研究进展.马钱子碱具有多个官能团和复杂的立体结构,对其进行选择性结构修饰极具挑战性.目前已有多种方法实现了在其特定位点的选择性反应,具体包括:芳环部分的脱甲氧基五氟苯基化,酰胺部分的伯胺缩合、脱氧氰基化、脱氧还原、α-肟化等反应,叔胺部分的N-氧化、C—N或α-C—H键的形式上卡宾插入、与苯炔和酚的三组分反应、与乃春的N-胺负离子化和与卤代烃的N-烃基化等反应,C=C双键的双羟基化和氢化反应,醚键的氢化断裂反应.其修饰后的结构具有独特的生物活性和潜在的药用价值.马钱子碱本身可作为手性拆分试剂,对外消旋的羧酸、磷(膦)酸、酚、醇和药物进行拆分.此外,马钱子碱及其结构修饰产物均可作为手性助剂、手性催化剂或手性配体运用到不对称合成中.

The recent advances on the structural modifications and chiral applications of Brucine are reviewed.Brucine is a naturally occuring molecule with multiple functional groups and a complex stereochemical structure.Selective structural modification of brucine is challenging,and a variety of methods to achieve selective modifications at its specific site are available.The aryl moiety undergoes demethoxypenta fluorophenylation,and the amide moiety undergoes the condensation with primary amine,deoxycyanation,deoxygenative reduction,andα-oximation.The tertiary amine moiety undergoes N-oxidation,formal carbene insertions of C—N orα-C—H bonds,three-component reactions with benzynes and phenols,N-amidation with nitrene,and N-alkylation with halogenated hydrocarbons.The C=C subunit undergoes dihydroxylation and hydrogenation,while the ether subunit undergoes hydrogenative cleavage.The modified structures have high potential medicinal values.As a chiral resolution reagent,brucine has been widely used in the resolution of racemic carboxylic acids,phosphoric or phosphonic acids,phenols,alcohols and some drugs.Additionally,brucine and its modified structures also find applications as chiral auxiliaries,chiral catalysts or chiral ligands in asymmetric synthesis and catalysis.