Stereoselective synthesis of Z-acrylonitrile derivatives: catalytic and acetylcholinesterase inhibition studies

作者：Parveen Mehtab^*; Malla Ali Mohammed; Alam Mahboob; Ahmad Musheer; Rafiq Shahnawaz

来源：New Journal of Chemistry, 2014, 38(4): 1655-1667.

DOI：10.1039/c3nj01384g

In the present study, a focused library of (Z)-acrylonitrile analogues (library A %26 B) were synthesized, which were typically accessed via a facile Knoevenagel condensation between p-nitrophenylacetonitrile and appropriately substituted aromatic aldehydes (1a-i) and 3-formyl chromones (3a-c). This new synthetic eco-friendly approach resulted in a remarkable improvement in the synthetic efficiency (83-92% yield), high purity, minimizing the production of chemical wastes without using highly toxic reagents for the synthesis and, more notably, it improved the selectivity for (Z)-acrylonitrile derivatives. By performing DFT calculations, it was found that the (Z)-isomer of compound 2b is stabilized by 2.61 kcal mol(-1) more than the (E)-isomer. All of the compounds were tested for acetylcholinesterase (AChE) inhibition. Compounds 2a and 4c, displayed the strongest inhibition, with IC50 values of 0.20 mu M and 0.22 mu M respectively. The methoxy group at the para-position of phenyl ring A was found to be essential for AChE inhibition.

• 出版日期2014