Phosphamide mustard

Enzyme catalyzed oxidation of cyclophosphamide yields 4-hydroxy cyclophosphamide (e) and subsequent formation of aldophosphamide (f) that leads to phosphamide mustard (g) which is considered to be the ultimate alkylating agent. 

A novel photo activated phosphamide mustard prodrug (70) equipped with a new type of photolabile carbonyl-protecting group has been designed and synthesized by group of Wang and Mondal. ... 

In most species, cyclophosphamide is rapidly absorbed, metabolized, and excreted. In patients, cyclophosphamide was distributed rapidly to all tissues and exhibited a half-life of 6.5-7h. The majority of an administered dose (50-68%) was excreted in the urine and no parent compound or metabolite was detected in expired air or feces. Carboxyphosph-amide and phosphoramide mustard were detected in the urine. Cyclophosphamide is a racemer, and stereoselective metabolism by cytochrome P-450 of the enantiomers has been demonstrated in mice, rats, and rabbits. The primary metabolite is the 4-hydroxy derivative, and it exists in equilibrium with aldo-phosphamide, its ring-opened tautomer. Either metabolite can be converted by mammalian enzymes to 4-ketocyclophosphamide or to the propionic derivative. Both metabolites are relatively nontoxic and represent major urinary metabolites. 

Arnold, H., Bourseaux, R, Brock, N. Chemotherapeutic action of a cyclic nitrogen mustard phosphamide ester (B518-ASTA) in experimental tumors of the rat. Nature 1958, 181, 931. 

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