ISSN:
0749-1581
Keywords:
Cyclophosphamides
;
1H NMR
;
13C NMR
;
31P coupling constants
;
Molecular modelling
;
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
High-field NMR studies at 11.7 T of newly synthesized diastereomeric 1-aza-2-bis(2-chloroethyl)amino-3-oxa-2- oxo-2-phospha-7-thia-bicyclo[4.4.0]decanes (4, 5) and the corresponding [4.3.0]nonanes (6, 7) were carried out by employing a combination of one- and two-dimensional homo- and heteronuclear methods. Unambiguous 31P, 1H and 13C chemical shift assignments for these bicyclic derivatives of cyclophosphamide were obtained, and the spin-spin couplings involving 1H, 13C and 31P were analysed in detail to determine the stereochemistry. Particularly useful were 1H J-resolved experiments, which separated phosphorus-proton couplings from proton-proton couplings, and 1H—13C shift-correlation experiments, which resolved the carbon-phosphorus couplings and provided information on the relative signs of J(P, H) and J(P,C). In addition, extensive molecular modelling calculations using various force-field (ALCHEMY, DISCOVER) and molecular orbital methods (MNDO, AM1, PM3) were carried out, and improved parameters for cyclophosphamides were developed for ALCHEMY. The diastereomeric pairs 4, 5 and 6, 7 differ in the axial vs. equatorial orientation of the sulphur substituent on the oxazaphosphorinane ring, which is itself exclusively in a chair conformation with axial P=O for all substances.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/mrc.1260301212
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