SignificanceThe most widely used antimalarial drugs belong to the quinoline family. The question of their mode of action has been open for centuries. It has been recently narrowed down to whether these drugs interfere with the process of crystallization of heme in the malaria parasite. To date, all studies of the drug action on heme crystals have been done either on model systems or on dried parasites, which yielded limited data and ambiguity. This study was done in actual parasites in their near-native environment, revealing the mode of action of these drugs in vivo. The approach adopted in this study can be extended to other families of antimalarial drugs, such as artemisinins, provided appropriate derivatives can be synthesized.
We report a Michael-type
cyanation reaction of coumarins by
using CO2 as a catalyst. The delivery of the nucleophilic
cyanide was realized by catalytic amounts of CO2, which
forms cyanoformate and bicarbonate in the presence of water. Under
ambient conditions, CO2-catalyzed reactions afforded high
chemo- and diastereoselectivity of β-nitrile carbonyls, whereas
only low reactivities were observed under argon or N2.
Computational and experimental data suggest the catalytic role of
CO2, which functions as a Lewis acid, and a protecting
group to mask the reactivity of the product, suppressing byproducts
and polymerization. The utility of this convenient method was demonstrated
by preparing biologically relevant heterocyclic compounds with ease.
Transamidation reactions are often mediated by reactive substrates in the presence of overstoichiometric activating reagents and/or transition metal catalysts. Here we report the use of CO 2 as a traceless catalyst: in the presence of catalytic amounts of CO 2 , transamidation reactions were accelerated with primary, secondary, and tertiary amide donors. Various amine nucleophiles including amino acid derivatives were tolerated, showcasing the utility of transamidation in peptide modification and polymer degradation (e.g., Nylon-6,6). In particular, N,O-dimethylhydroxyl amides (Weinreb amides) displayed a distinct reactivity in the CO 2 -catalyzed transamidation versus a N 2 atmosphere. Comparative Hammett studies and kinetic analysis were conducted to elucidate the catalytic activation mechanism of molecular CO 2 , which was supported by DFT calculations. We attributed the positive effect of CO 2 in the transamidation reaction to the stabilization of tetrahedral intermediates by covalent binding to the electrophilic CO 2 .
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.