手性药物分子绝对构型鉴定的理论研究进展

Progress of the theoretical research on absolute configuration assignment for chiral medicines

在手性药物研究过程中,绝对构型研究是非常重要的一步。随着计算方法的发展和软件的进步,利用不同的理论方法鉴定不同类型的手性分子的立体结构成为可能。这些方法主要包括手性分子的特征旋光值和旋光色散计算、手性分子矩阵方法中的特征值计算、电子圆二色谱计算、振动圆二色谱计算,将这些计算结果与实验值进行比较,能够很好地确定手性分子的绝对构型。目前,利用不同的计算方法交叉验证同一分子的立体结构,已成为一个非常有效的研究模式。此外,利用简化模型用于计算也是一个关键和普遍的方法。首次详细分析了使用简化模型背后的关键科学问题,介绍了新的“构象对”的理论概念。

It is very important to assign a stereogenic center in study of the chiral medicines.With the development of calculation methods and software, it is possible to use different theoretical methods to assign the absolute configuration of chiral compounds.Now, the methods are used for different calculation, such as specific optical rotation, optical rotatory dispersion, determinant in matrix of chiral compound, electronic circular dichroism and vibrational circular dichroism.The stereogenic centers can be determined by comparing the theoretical values with the experimental data.Until now, it has become a popular way by using two or more theoretical methods in absolute configuration determination.On the other hand, it is a key and popular method to use a simplified model to replace a complex chiral compound in various calculations.This review analyzed the fundamental science and introduced a new concept of “conformer pair” for the first time.