Research on development of efficient chirality alternation methods under thermodynamic conditions

我们研究了[14]对吡啶衍生物的异构化性质，并证明了结晶诱导和吸附诱导的不对称转化分别是在平面手性[14]对吡啶衍生物中形成相反立体化学意义的有效方法。我们还发现，阿扎斯匹林类似物具有其特有的螺旋骨架，在中性水介质中容易发生外消旋，并且通过使用适当的手性助剂，通过对每个非对映异构体进行酸性水解来解决类似物，从而获得高富集对映异构体的阿扎斯匹林类似物，在不损失其过量对映异构体的情况下，以优异的收率获得高富集对映异构体。顺序转化为对映纯类似物及其外消旋体的再循环过程实现了阿扎斯匹林旋光类似物的有效合成途径。

We have investigated isomerization properties of [14]parapyridinophane derivatives and demonstrated that crystallization-induced and adsorption-induced asymmetric transformations are efficient protocols to prefer the opposite sense of stereochemistry in planar-chiral [14]parapyridinophane derivatives, respectively. We have also found that azaspirene analog having its characteristic spiro skeleton readily undergoes racemization in neutral aqueous media and that efficient resolution was achieved by using an appropriate chiral auxiliary to resolve the analog by the following acidic hydrolysis of each diastereoisomer to afford highly enantio-enriched azaspirene analog in excellent yields without a loss of their enantiomeric excesses. The sequential transformation to enantiomerically pure analog and its recycling process to its racemic body achieved an efficient synthetic route to an optically active analog of azaspirene.