Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, Pisa 56126, Italy.
J Comput Chem. 2010 Nov 15;31(14):2612-9. doi: 10.1002/jcc.21556.
Azidolysis of epoxides followed by reduction of the intermediate azido alcohols constitutes a valuable synthetic tool for the construction of beta-amino alcohols, an important chemical functionality occurring in many biologically active compounds of natural origin. However, depending on conditions under which the azidolysis is carried out, two regioisomeric products can be formed, as a consequence of the nucleophilic attack on both the oxirane carbon atoms. In this work, predictive models for quantitative structure-reactivity relationships were developed by means of multiple linear regression, k-nearest neighbor, locally weighted regression, and Gaussian Process regression algorithms. The specific nature of the problem at hand required the creation of appropriate new descriptors, able to properly reflect the most relevant features of molecular moieties directly involved in the opening process. The models so obtained are able to predict the regioselectivity of the azidolysis of epoxides promoted by sodium azide, in the presence of lithium perchlorate, on the basis of steric hindrance, and charge distribution of the substituents directly attached to the oxirane ring.
环氧化合物的叠氮裂解，随后还原中间的叠氮醇，构成了构建β-氨基醇的有价值的合成工具，β-氨基醇是许多天然来源的生物活性化合物中重要的化学官能团。然而，根据叠氮裂解进行的条件不同，由于亲核进攻两个环氧化物碳原子，可以形成两种区域异构体产物。在这项工作中，通过多元线性回归、k-最近邻、局部加权回归和高斯过程回归算法开发了定量结构-反应性关系的预测模型。手头问题的特殊性质要求创建适当的新描述符，能够正确反映直接参与开环过程的分子部分的最相关特征。由此获得的模型能够根据与环氧化物环直接相连的取代基的空间位阻和电荷分布，预测在高氯酸锂存在下由叠氮化钠促进的环氧化合物的区域选择性叠氮裂解。
