Application of rhodium-catalyzed cyclohydrocarbonylation to the syntheses of enantiopure homokainoids

Abstract

Kainic acid, rigidified (S)-glutamic acid, is a well-known kainite receptor agonist for the excitatory transmission in the central nerve system. Our interest in highly selective kainite ligands, prompted us to design a series of new kainic homologues, "homokainoids", i.e., conformationally rigidified (S)-glutamic acids. For the syntheses of enantiopure novel homokainoids (pipecolinoglutamic acids), we successfully applied cyclohydrocarbonylation (CHC) reaction that has been developed in these laboratories. Efficient total syntheses of enantiopure novel homokainoids from (R)-serine feature the highly diastereoselective conjugate addition and the regioselective CHC process in the key steps.

Carbonylations of Alkenes in the Total Synthesis of Natural Compounds

“…through use of a tandem hydroformylation-condensation reaction. 53 These rigidified derivatives of glutamic acid were to be tested for their effect on glutamate receptors, which are thought to be possible starting points for the treatment of disorders like stroke, epilepsy, Alzheimer's or Parkinson's disease. Starting from (R)-serine (97), the carbonylation substrates were produced through a sequence of seven or eight steps, respectively (Scheme 19).…”

Synthesis, receptor binding and activity of iso and azakainoids

“…10 The syntheses, but not the biological activity of homokainoids was recently described. 11 Currently there is no information on the effect of replacing the C-5 methylene with nitrogen (azakainoids) or translocation of nitrogen relative to the ring substituents (isokainoids). Herein we report the first syntheses of unsubstituted aza 3 and isokainoid 4 as well as preliminary receptor binding and activity studies.…”

A Synthesis of Pseudoconhydrine and Its Epimer via Hydroformylation and Dihydroxylation

“…In terms of tons of product per year, hydroformylation is probably the largest transition metal-catalyzed process in current operation. − The reaction is used for the synthesis of huge amounts of bulk chemicals but has received less attention from synthetic organic chemists . Notable exceptions are found in the work of Ojima and, more recently, Breit, as well as Taddei and Mann, and Tan . An advantage of hydroformylation for the synthesis of complex molecules is the good tolerance of other functional groups by the reaction.…”