Chemical synthesis of the (1R,2S) and (1S,2R) arene oxide metabolites of acridine

Abstract

Enantiopure samples of (+)-(1R,2S) and (–)-(1S,2R)-1,2-epoxy-1,2-dihydroacridine 4 have been obtained from the corresponding trans-2-bromo-1,2,3,4-tetrahydroacridin-1-ol MTPA esters 7a and b. Absolute configurations were deduced by stereochemical correlation to (+)-(1R,2R)-trans-2-bromo-1-(2-methoxy-2-phenyl-2-trifluoroacetoxy)-1,2,3,4-acridine 7a which was unequivocally assigned by X-ray crystal structure analysis. (–)-(1R,2R)-trans-1,2-Dihydroacridine-1,2-diol 2 was obtained by alkaline hydrolysis of (+)-(1R,2S)-acridine 1,2-oxide 4.