Bosica Giovanna, Demanuele Kaylie, Padrón José M, Puerta Adrián
Department of Chemistry, University of Malta, Msida, MSD 2080 Malta.
BioLab, Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Universidad de La Laguna, c/Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain.
Beilstein J Org Chem. 2020 Nov 24;16:2862-2869. doi: 10.3762/bjoc.16.235. eCollection 2020.
A rapid route for obtaining unsymmetrical 1,2-dihydropyridines (1,2-DHPs) as opposed to 1,4-dihydropyridines (1,4-DHPs) has been achieved via a one-pot multicomponent Hantzsch reaction. A benign protocol has been developed for the preparation of various 1,2-dihydropyridine derivatives using heterogenized phosphotungstic acid on alumina support (40 wt %). High yields of over 75% have been accomplished in just 2-3.5 h after screening several heterogeneous catalysts and investigating the optimal reaction conditions. The catalyst chosen has passed the heterogeneity test and was shown to have the potential of being reused for up to 8 consecutive cycles before having a significant loss in activity. In addition, aromatic aldehydes gave the aforementioned regioisomer while the classical 1,4-DHPs were obtained when carrying out the reaction using aliphatic aldehydes. The preliminary study of the antiproliferative activity against human solid tumor cells demonstrated that 1,2-DHPs could inhibit cancer cell growth in the low micromolar range.
通过一锅多组分汉茨希反应，已实现了一条与1,4 - 二氢吡啶（1,4 - DHPs）相对的获取不对称1,2 - 二氢吡啶（1,2 - DHPs）的快速路线。已开发出一种良性方案，用于使用负载在氧化铝载体（40重量%）上的均相磷钨酸制备各种1,2 - 二氢吡啶衍生物。在筛选了几种多相催化剂并研究了最佳反应条件后，仅在2 - 3.5小时内就实现了超过75%的高产率。所选择的催化剂通过了多相性测试，并且显示出在活性显著损失之前能够连续重复使用多达8个循环的潜力。此外，芳香醛生成上述区域异构体，而使用脂肪醛进行反应时则得到经典的1,4 - DHPs。对人实体瘤细胞的抗增殖活性的初步研究表明，1,2 - DHPs在低微摩尔范围内可抑制癌细胞生长。
