title: Spectroscopic detection of iminocyclophosphamide and its possible role in cyclophosphamide metabolism.
abstract: Iminocyclophosphamide (4) has been identified by 1H NMR as a product from base treatment of 4-alkylthio-substituted cyclophosphamide derivatives, viz., cis-4-(propylthio)cyclophosphamide (cis-7). A maximum concentration of approximately 12% of total product was observed by treating cis-7 with ethyl propiolate and NaH or deuteriated dimsyl anion in anhydrous Me2SO-d6. Treatment of cis-7 with base alone established a rapid cis-/trans-7 equilibrium via the imine intermediate 4. Base-catalyzed expulsion of 1-propanethiol (8) from cis-7 and thiol trapping afforded formation of 4, which subsequently underwent elimination to the relatively more stable conjugated (vinylimino)-phosphamide (9). Iminocyclophosphamide (4) was also identified by fast atom bombardment mass spectrometry as a product generated upon analysis of cyclophosphamide derivatives substituted in the 4-position of the oxazaphosphorine ring with various leaving groups.
mesh_terms: D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
chemical_list: C035963:iminophosphamide; D003520:Cyclophosphamide