title: Diastereoselective synthesis of potent antimalarial cis-β-lactam agents through a [2 + 2] cycloaddition of chiral imines with a chiral ketene.
abstract: The effect of double asymmetric induction for the synthesis of new cis-β-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-β-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 μM. Of the fifteen β-lactams tested, four showed IC50 ≤ 11 μM.
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Iran. Electronic address: aliasghar6683@yahoo.com.
authors.forename: Aliasghar
authors.initials: A
authors.lastname: Jarrahpour
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Iran.
authors.forename: Edris
authors.initials: E
authors.lastname: Ebrahimi
authors.affiliation: Aix-Marseille Université, UMR-MD3 Relation hôte-parasites, Physiopathologie & Pharmacologie, Faculté de pharmacie, Bd Jean Moulin, F-13385 Marseille, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Sinou
authors.affiliation: Aix-Marseille Université, UMR-MD3 Relation hôte-parasites, Physiopathologie & Pharmacologie, Faculté de pharmacie, Bd Jean Moulin, F-13385 Marseille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Latour
authors.affiliation: Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS, UMR7258, Institut Paoli Calmettes, Aix-Marseille Université, UM 105, Inserm, U1068, Faculté de pharmacie, Bd Jean Moulin, F-13385 Marseille, France.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Brunel
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D061565:Cycloaddition Reaction; D005030:Ethylenes / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D005030:Ethylenes; D007097:Imines; D007659:Ketones; D047090:beta-Lactams; C008223:ketene
keywords: Antimalarial activity; Chiral imine; Chiral ketene; Diastereoselective; Staudinger reaction; β-lactam