2-Phenyl-3-(quinolizidin-1-yl)-5-substituted indoles as platelet antiaggregating agents

Indolizidine and quinolizidine alkaloids

“…Miscellaneous synthetic transformations of interest include the vinylation of lupinine 315 with acetylene in a superbasic medium to give the vinyl ether 338 (for example, with potassium tert-butoxide in dimethyl sulfoxide at 105-110 • C; yield, 88%); 122 the synthesis of a large range of lupinine and epilupinine derivatives such as 339, among many others, for testing as ligands for sigma receptors in the central nervous system, which are implicated in the pathogenesis of psychiatric and motor disorders; 123 and the Fischer indolisation of the lupinyl and epilupinyl phenyl ketones 340, prepared from the parent alkaloids during a search for novel inhibitors of platelet aggregation. 124…”

Total Synthesis of (+)-Epilupinine via An Intramolecular Nitrile Oxide-Alkene Cycloaddition

“…In recent years, it has been widely employed as intermediates or pharmacophores in drug discovery. Many molecules bearing epilupinyl unit are potential ligands for 5-HT 3 , 5-HT 4 or Sigma receptors as well as antiviral, antiarrhythmic, antimalarial or platelet antiaggregating agents . Since its typical structure and biologically important properties, especially the fact that it often served as an excellent vehicle for the validation of new synthetic methodology and strategy, (+)-epilupinine ( 2 ) has attracted great interest as a challenging target for total synthesis.…”

A Concise Asymmetric Total Synthesis of (+)-Epilupinine

“…1 has been known to exhibit in vitro inhibitory activity against Leukaemia P-388 and lymphocytic Leukaemia L1210 . Recent studies elucidated that the structure of 1 incorporated into various drugs plays an important role as a pharmacophore . For example, the (+)-epilupinine moiety of antiviral and antimalarial drugs is suggested to behave as a ligand of 5-HT 3 , 5-HT 4 , and sigma receptors .…”