S. Ludeman, E. M. Shulman-Roskes, M. P. Gamcsik
Apr 1, 1993
Citations
0
Influential Citations
10
Citations
Journal
Journal of Labelled Compounds and Radiopharmaceuticals
Abstract
The cyclophosphamide metabolite phosphoramide mustard (PM) was synthesized with isotopic enrichment at each nitrogen and oxygen site. Sequential reaction of N,N-bis(2-chloroethyl)phosphoramidic dichloride [Cl2P(O)N(CH2CH2Cl)2] with benzyl 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 (CHA) provided PM as the CHA salt. Incorporation of 15NH3 into this general scheme gave PM with a 15NH2 moiety. Glycine-15N was converted to bis(2-chloro-ethyl)amine-15N hydrochloride which, in turn, provided for N,N-bis(2-chloroethyl)phosphoramidic-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-17O. To obtain the alcohol, labelled benzaldehyde was made by exchange with 17OH2 and was then reduced with sodium borohydride.