Diastereoselective synthesis of potent antimalarial cis-beta-lactam agents through a [2+2] cycloaddition of chiral imines with a chiral ketene

作者：Jarrahpour Aliasghar^*; Ebrahimi Edris; Sinou Veronique; Latour Christine; Brunel Jean Michel

来源：European Journal of Medicinal Chemistry, 2014, 87: 364-371.

DOI：10.1016/j.ejmech.2014.09.077

• beta-lactam
• Chiral imine
• Chiral ketene
• Staudinger reaction
• Diastereoselective
• Antimalarial activity

The effect of double asymmetric induction for the synthesis of new cis-beta-lactams by [2 + 2] cycloaddition reactions of chiral imines with a chiral ketene was investigated. The cycloaddition reaction was found to be totally diastereoselective leading exclusively to the formation of the cis-beta-lactam derivatives. The newly synthesized cycloadducts were evaluated for their antimalarial activities against Plasmodium falciparum K14 resistant strain with moderate to excellent IC50 values varying from 8 to 50 mu M. Of the fifteen beta-lactams tested, four showed IC50 %26lt;= 11 mu M.

• 出版日期2014-11-24