ABSTRACT
Securinine, an alkaloid originally isolated from Securinega suffruticosa, exhibits a wide range of biological activities, including anti-malarial activity. Along with securinine, 10 pyrrolidine derivatives, generated via the retrosynthesis of (-)-securinine, were selected and tested for their inhibitory activity against Toxoplasma gondii growth in vitro. Anti-Toxoplasma activity correlated to hydrophobicity of the tested compounds. Three pyrrolidine derivatives along with securinine inhibit Toxoplasma proliferation at the micromolar range. These compounds act on parasite proliferation in different capacities, either by slowing the growth rate or inhibiting invasion of host cells. Securinine induces bradyzoite differentiation at comparable levels to treatment with alkali media in vitro.
Subject(s)
Antiprotozoal Agents/pharmacology , Azepines/pharmacology , Lactones/pharmacology , Piperidines/pharmacology , Pyrrolidines/pharmacology , Toxoplasma/drug effects , Antiprotozoal Agents/chemistry , Azepines/chemistry , Cells, Cultured , Fibroblasts/drug effects , Fibroblasts/parasitology , Foreskin/cytology , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Heterocyclic Compounds, Bridged-Ring , Humans , Lactones/chemistry , Male , Piperidines/chemistry , Pyrimethamine/pharmacology , Pyrrolidines/chemistry , Toxoplasma/growth & developmentABSTRACT
The alkaloid (-)-securinine was synthesized in 18 steps and 16% overall yield from trans-4-hydroxy-l-proline.
Subject(s)
Azepines/chemical synthesis , Lactones/chemical synthesis , Piperidines/chemical synthesis , Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Heterocyclic Compounds, Bridged-Ring , StereoisomerismABSTRACT
A variety of aryl and heteroaryl bromides were cross-coupled with ammonia in good to high yields in the presence of a copper-NHC catalyst.
ABSTRACT
Acyclic diaminocarbenes are found to be useful ligands for palladium catalyzed Suzuki-Miyaura, Sonogashira and Heck cross-coupling reactions of aryl/alkenyl bromides and chlorides.
ABSTRACT
A wide variety of tertiary carbinamines are synthesized in high yields via diastereoselective allylation and crotylation of in situ generated N-unsubstituted ketimines.
