Enantioselective synthesis of encecaline-derived potent antimalarial agents

Harel, Dipak and Schepmann, Dirk and Brun, Reto and Schmidt, Thomas J. and Wünsch, Bernhard. (2013) Enantioselective synthesis of encecaline-derived potent antimalarial agents. Organic & biomolecular chemistry : an international journal of synthetic, physical and biomolecular organic chemistry, Vol. 11, H. 42. pp. 7342-7349.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6194656

Downloads: Statistics Overview


The high antiplasmodial activity of racemic benzylamines rac-1 and rac-2 stimulated the synthesis of pure enantiomers. Ellman's chiral sulfinamides (S)-6 and (R)-6 were used as chiral auxiliaries. Condensation of prochiral ketone 5 with enantiomerically pure sulfinamides (S)-6 and (R)-6 and subsequent NaBH4 reduction provided predominantly unlike configured diastereomers (S,R)-8 and (R,S)-8 (ratio unlike-8:like-8 = 90:10). The same transformation of phenol 4 led to the diastereomeric sulfinamides (S,R)-12 and (S,S)-12 in the ratio 60:40. Acid hydrolysis of the diastereomerically pure sulfinamides followed by monobenzylation yielded the enantiomerically pure benzylamines (R)-1, (S)-1, (R)-2 and (S)-2. The enantiomeric purity of the products was proven by chiral HPLC and the absolute configuration by CD-spectroscopy. Generally, benzylamines with (R)-configuration show higher antiplasmodial activity than their corresponding (S)-configured enantiomers. Phenol (R)-2 represents a very potent lead against P. falciparum, with an IC50 value of only 0.026 μM against the NF54 strain. The very high eudismic ratio of 34 indicates the enantioselective interaction of phenol (R)-2 with a particular target protein of P. falciparum.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Brun, Reto
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Royal Society of Chemistry
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:31 Jan 2014 09:49
Deposited On:31 Jan 2014 09:49

Repository Staff Only: item control page