Stereospecific synthesis of chiral metabolites of ifosfamide and their determination in the urine
- 30 April 1983
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 26 (5) , 674-679
- https://doi.org/10.1021/jm00359a010
Abstract
The stereospecific synthesis of 2 chiral metabolites of ifosfamide (2) [an antitumor agent], 4-ketoifosfamide and 2-amino-3-(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide is reported. The absolute configuration of both compounds was assigned on the basis of chemical correlation. In addition, 2 other achiral metabolites of 2, carboxyifosfamide and IPAM [N,N''-bis(2-chloroethyl)phosphorodiamidic acid], were synthesized. These and other organophosphorus metabolites of ifosfamide were found, by 31P NMR, in the urine of patients to whom racemic 2 was administered. The measurements performed in the presence of an optically active lanthanide shift reagent showed considerable stereoselectivity of in vivo formation of some chiral metabolites of ifosfamide.This publication has 7 references indexed in Scilit:
- Comparative study on human pharmacokinetics of activated ifosfamide and cyclophosphamide by a modified fluorometric testZeitschrift für Krebsforschung und Klinische Onkologie, 1981
- The synthesis of enantiomers of 4-ketocyclophosphamideCellular and Molecular Life Sciences, 1981
- QUANTIFICATION BY GAS-CHROMATOGRAPHY OF N,N'-DI-(2-CHLOROETHYL)-PHOSPHORODIAMIDIC ACID IN THE PLASMA OF PATIENTS RECEIVING ISOPHOSPHAMIDE1980
- Synthesis and absolute configuration assignments of enantiomeric forms of ifosphamide, sulfosphamide, and trofosphamideJournal of the American Chemical Society, 1979
- Stereospecific synthesis of (R)- and (S)-isophosphamideThe Journal of Organic Chemistry, 1979
- Determination of Enantiomeric Homogeneity (Optical Purity) of Cyclophosphamide by Nuclear Magnetic Resonance Spectroscopy 2JNCI Journal of the National Cancer Institute, 1977
- Synthesis and absolute configuration of the optically active forms of 2-[bis(2-chloroethyl)amino]-4-methyltetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide (4-methylcyclophosphamide)The Journal of Organic Chemistry, 1977