STEREOSPECIFIC SYNTHESIS OF TETRADEUTERATED (R)-IFOSFAMIDE AND (S)-IFOSFAMIDE

The tetradeuterated analogues of (R)- and (S)-ifosfamide [(S)- and (R) -2-(2-chloro-2,2-dideuterioethyl) terio-tetrahydro-2H-1,3,2-oxazaphosp horin-2-oxide, (S) and (R)-1-d(4)] were synthesized by modification of a literature procedure. The enantiomers of alpha-methylbenzylamine we re employed as the resolving agents in the multi-step synthesis in a 9 % overall yield. The selected labeled positions should minimize potent ial isotope effects useful for the investigation of stereoselective me tabolism of ifosfamide by pseudoracemate methodology.