01976nas a2200193   4500008004100000022001400041245016700055210006900222260000900291300001600300490000600316520122200322100002601544700001901570700002001589700001801609700002801627856012701655       2020                        eng d  a2470-134300aEnantioselective synthesis of gamma-phenyl-gamma-amino vinyl phosphonates and sulfones and their application to the synthesis of novel highly potent antimalarials0 aEnantioselective synthesis of gammaphenylgammaamino vinyl phosph  cNOV   a29025-290370 v53 a<p>Racemic and enantioselective syntheses of gamma-phenyl-gamma-amino vinyl phosphonates and sulfones have been achieved using Horner-Wadsworth-Emmons olefination of trityl protected alpha-phenyl-alpha-amino aldehydes with tetraethyl methylenediphosphonate and diethyl ((phenylsulfonyl)methyl)phosphonate, respectively, without any racemization. The present strategy has also been successfully applied to the synthesis of peptidyl vinyl phosphonate and peptidyl vinyl sulfone derivatives as potential cysteine protease inhibitors of Chagas disease, K11002, with 100% de. The developed synthetic protocol was further utilized to synthesize hybrid molecules consisting of artemisinin as an inhibitor of major cysteine protease falcipain-2 present in the food vacuole of the malarial parasite. The synthesized artemisinin-dipeptidyl vinyl sulfone hybrid compounds showed effective in vitro inhibition of falcipain-2 and potent parasiticidal efficacies against Plasmodium falciparum in nanomolar ranges. Overall, the developed synthetic protocol could be effectively utilized to design cysteine protease inhibitors not only as novel antimalarial compounds but also to be involved in other life-threatening diseases.</p>
1 aAratikatla, Eswar, K.1 aKalamuddin, Md1 aMalhotra, Pawan1 aMohmmed, Asif1 aBhattacharya, Asish, K.  uhttps://library.ncl.res.in/content/enantioselective-synthesis-gamma-phenyl-gamma-amino-vinyl-phosphonates-and-sulfones-and