252898-26-3Relevant academic research and scientific papers
A novel and efficient synthesis of a highly active analogue of clasto-lactacystin β-lactone
Soucy, Francois,Grenier, Louis,Behnke, Mark L.,Destree, Antonia T.,McCormack, Teresa A.,Adams, Julian,Plamondon, Louis
, p. 9967 - 9976 (2007/10/03)
Herein, we describe a new convergent synthesis of a more potent analogue of clasto-lactacystin β-lactone (2), PS-519 compound 4, which is currently in preclinical development for the treatment of ischemia-reperfusion injury in stroke and myocardial infarction. The synthetic strategy relies on building two intermediates (an oxazoline and an aldehyde) which are joined through a doubly diastereoselective aldol reaction, setting up the requisite unichiral centers in the final product (4). The facial selectivity and ultimate stereocontrol are achieved by employing a trivalent aluminum Lewis acid, Me2AlCl, in a chelation-induced reaction which yields a single aldol adduct. The efficiency of the synthetic approach has allowed for the preparation of multigram quantities of clinical grade material, which will support Phase I studies.
