항암제인 Cyclophosphamide의 중간체인 15N과 17O-phosphoramide Mustards의 합성

The Study of Cyclophosphamide Metabolite 15N and 17O Phosphoramide Mustards

Each nitrogen and oxygen site isotope enriched the cyclophosphamide metabolite phosphoramide mustard was synthesized. Reaction of N,N-bis(2-chloroethyl)phosphoramidic dichloride [Cl2P(O)N(CH2CH2Cl)2] with benzy] alcohol and ammonia gave N,N-bis(2-chloroethyl)phosphorodiamidic acid phenylmethyl ester [BzO(H2N)P(O)N(CH2CH2Cl)2]. Catalytic hydrogenation of this benzyl ester followed by the addition of cyclohexylamine provided PM. Incorporation of 15-NH3 into this general scheme gave PM with a 15NH2 moiety. Glycine-15N was converted to bis(2-chloroethyl)amine-15N hydrochloride which, in turn, provided for N,N-bis(2-chloroethyl)phosphorodiamidic-15N dichloride. Use of this compound in the general synthetic pathway yielded PM.CHA with 15N in the mustard moiety. 17O-Enriched PM was generated through the use of benzyl alcohol-170. To obtain the alcohol, labelled benzaldehyde was made by exchange with 17-OH2 and was then reduced with sodium borohydride.