SYNTHESIS METHOD FOR PRODUCING ENANTIOMERICALLY PURE CIS-IMIDAZOLINE COMPOUNDS FOR PHARMACEUTICAL USE

摘要

This invention provides a method for enantioselective synthesis of cis-imidazolines andrelated structures through chiral resolution. A chiral acid is used toseparate enantiomeric precursorsof the cis-imidazolines from a racemic mixture by selective ciystallization.By way of illustration, themethod comprises use of a racemic mixture of a precursor according to Formula(A):(See Formula A)Both enantiomers can be cyclized into the desired cis-imidazoline bycomplementary pathways.Compounds can be synthesized according to the invention with an enantiomericexcess as high as99%. Cis-imidazolines such as Nutlin-3a prepared according to this inventionmay be used fortreating cancer, killing senescent cells, or treating senescence-associatedconditions.