Organic and Biomolecular Chemistry p. 7342 - 7349 (2013)
Update date:2022-08-16
Topics:
Harel, Dipak
Schepmann, Dirk
Brun, Reto
Schmidt, Thomas J.
Wuensch, Bernhard
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 NaBH 4 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.
View MoreContact:+86-27-67841589
Address:Add: 999 Gaoxin Road, Donghu New Technology Development Zone, Wuhan City, Hubei, China
Tianjin Pharmacn Medical Technology Co.,Ltd.
Contact:86-22-60122566ext.866(English),23359620
Address:Green Industrial Base, 6 Haitaifazhan Sixth Rd., Huayuan Industrial Area, Tianjin, 300384, China
Liaoyang Xinyou Chemical Products Co.,Ltd.
Contact:+86-419-5165433 13604191870
Address:Huishang Road6-1, Hongwei District, Liaoyang, Liaoning, China
Shanghai Dynamic Industrial Co.,Ltd.
website:http://www.shdynamic.com
Contact:86-021 3392 6680
Address:Room 805 Information Tower, No.1403 Minsheng Road, Pudong New Area, Shanghai 200135, P. R. China
Contact:+86 18616952870
Address:Area
Doi:10.1002/pola.27528
(2015)Doi:10.1021/j100456a005
(1980)Doi:10.1080/00397911.2013.806668
(2014)Doi:10.1080/00397919608003517
(1996)Doi:10.1021/jacs.7b12707
(2018)Doi:10.1063/1.106898
(1992)