Solid-phase synthesis and bioevaluation of Lupeol-based libraries as antimalarial agents

The use of the triterpenoid lupeol as a scaffold for the synthesis of lupeol-based libraries is described. Lupeol was anchored to a solid support (Rink amide/Sieber Amide) through aliphatic dicarboxylic acid moieties, which also served as a site for introducing diversity. The resulting polymer linked 3β-O (resin-alkanoyl)-lup-20(29)-ene 3 was used to generate key intermediates 3β-O (resin-alkanoyl)-30-bromo-lup-20(29)-ene 4 and 3β-O (resin-alkanoyl)-30-amino-lup-20(29)-ene 6 for the generation of libraries based on disubstituted lupeol derivatives. A 96-member library was screened for its in-vitro antimalarial activity against Plasmodium falciparum.