Resolution, absolute configuration and antifilarial activity of coumarinyl amino alcohols

Abstract The resolution of racemic coumarinyl amino alcohols 5 – 10 was achieved by using the inexpensive and readily accessible chiral resolving agent N -carbethoxy- l -proline ( S )- 11 . Direct esterification of rac - 5 – 10 with ( S )- 11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols ( S )-(+)- 5 – 10 and ( R )-(−)- 5 – 10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins ( S )-(+)- 9 , ( R )-(−)- 9 and ( S )-(+)- 10 , ( R )-(−)- 10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10 , respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action.