Synthesis of 1-aldofosfamide-perhydrothiazines

Aldofosfamide-perhydrothiazine derivatives are a new class of prodrugs which spontaneously, with half-life times of 2 to > 12 h hydrolyse to the corresponding aldophosphamide in aquous solution. Synthesis of 1-aldofosfamide-perhydrothiazine (N,N'-(2-chloroethyl)-phosphorodiamide-2-(2'-[4'-carboxy-1',3'- perhydrothiazinyl])-ethylester) and a derivative, in which one 2-chlorethyl group of the alkylating function is substituted by a mesyl-ethyl-group (N-(2-Chloroethyl)-N'-(methanesulphonylethyl)- phosphorodiamide-2-(2'-[4'-carboxy-1',3'-perhydro-thiazinyl] )-ethylester), is described.