Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening
作者:Nassim Borazjani、Saghi Sepehri、Maryam Behzadi、Aliasghar Jarrahpour、Javad Ameri Rad、Maryam Sasanipour、Milad Mohkam、Younes Ghasemi、Amin Reza Akbarizadeh、Carole Digiorgio、Jean Michel Brunel、Mohammad Mehdi Ghanbari、Gyula Batta、Edward Turos
DOI:10.1016/j.ejmech.2019.06.036
日期:2019.10
Highly diastereoselective synthesis of chromeno β-lactam hybrids was achieved by an efficient one-pot three-component reaction. With this procedure, the desired β-lactam products were obtained in good yields and with exclusive cis stereoselection, by combining a variety of benzaldehydes, malononitrile, and either 5,5-dimethylcyclohexane-1,3-dione or 4-hydroxycoumarin in the presence of 1,4-diazabicyclo
通过高效的一锅三组分反应,实现了铬诺β-内酰胺杂合体的高度非对映选择性合成。通过这种方法,在存在下,通过将各种苯甲醛,丙二腈和5,5-二甲基环己烷-1,3-二酮或4-羟基香豆素结合使用,可以以高收率和独有的顺式立体选择获得所需的β-内酰胺产物在回流条件下得到1,4-二氮杂双环[2.2.2]辛烷。这些加合物的结构基于IR,1D和2D NMR光谱,X射线分析,H–H COZY和H–C HSQC二维NMR实验以及元素分析。筛选每种合成的化合物的抗炎和抗癌活性。β-内酰胺5b和8b分别显示出53.4和19.8的抗炎率,而5b则比用于治疗类风湿和皮肤炎症的众所周知的地塞米松皮质类固醇更有活性。β-内酰胺5a,5b,5e,5f,5g,8c,8j和8p也显示出对SW1116(结肠癌)细胞系的良好抗肿瘤活性,而对HepG2对照细胞系没有明显的细胞毒性。