Resolution, absolute configuration and antifilarial activity of coumarinyl amino alcohols

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. (C) 2017 Elsevier Ltd. All rights reserved.