174782-11-7Relevant articles and documents
Spontaneous Lossen Rearrangement of (Phosphonoformyl)hydroxamates. The Migratory Aptitude of the Phosphonyl Group
Salomon, Claudio J.,Breuer, Eli
, p. 3858 - 3861 (1997)
(i-PrO)2P(=O)COSEt (1) reacted with NH2OH in pyridine at room temperature to give mainly (i-PrO)2P(=O)NH2 (4). The formation of 4 was interpreted in terms of a spontaneous Lossen rearrangement of (i-PrO)2P(=O)CONHOH (2a) formed in the reaction. A transient 31P NMR signal appearing in the reaction mixture at δ-1.8 was assigned to 2a. Trapping of (i-PrO)2P(=O)N=C=O (5), formed in the reaction of 1 and NH2OH, by cyclohexylamine gave (i-PrO)2P(=O)NHCONHC6H11 (6). Attempted isolation of 6 gave the hydrolyzed product N-cyclohexylurea (7). The reaction of 1 with NH2OMe proceeded slower than that with NH2OH and gave the expected (i-PrO)2P(=O)-CONHOMe (2b), which was isolated and identified. 2b converts slowly to 4 in pyridine at room temperature. In contrast, MeNHOH reacted rapidly with 1 and gave the stable crystalline (i-PrO)2P(=O)CON(Me)OH (2c). The structure of hydroxamates 2 were assigned on the basis of 1H, 13C, and 31P NMR spectral data. This facile Lossen rearrangement is discussed in terms of the unusually high migratory aptitude of the phosphonyl group.
Compositions comprising oxophosphonate-based metalloproteinase inhibitors
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Page/Page column 13, (2008/06/13)
The present invention relates to compositions useful for treating or controlling disease states or conditions associated with zinc containing proteinases, especially metalloproteinases. The active ingredient in these compositions is an alpha-oxo- or alpha