CONFORMATIONAL STUDIES OF MUSCARONE ANALOGS - X-RAY-ANALYSIS AND MOLECULAR MECHANICS CALCULATIONS
Articolo
Data di Pubblicazione:
1992
Citazione:
CONFORMATIONAL STUDIES OF MUSCARONE ANALOGS - X-RAY-ANALYSIS AND
MOLECULAR MECHANICS CALCULATIONS / P.J. Carroll, M. De Amici, C. De Micheli, L. Toma. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 35:2(1992), pp. 305-309. [10.1021/jm00080a015]
Abstract:
The X-ray structure of muscarone analogues 3 and 4 was determined and
compared with that of muscarone (1, iodide and picrate salts), muscarine
2, dioxalane 5, oxathiolane 6, and tetrahydrofuran 7. In order to
better define the pharmacological stereoselectivity of muscarone, the
conformational profiles of compounds 1, 2, 3, and 5 were analyzed using
Allinger's MM2(85) progam or, in the case of 4, by H-1 NMR spectroscopy.
The conformation of the ring in 1 provided similar to that of the other
derivatives. MM2 calculations predicted a preferred gauche arrangement
of the sides chain for 1 and its analogues; such an arrangement was also
observed in the solid state of muscarone picrate. Thus, the
antiperiplanar arrangement reported for crystaline muscarone iodide
appears to be due to crystallographic packaging forces. As a
consequence, the rationalization of the phasrmacological profile of 1
based on the antiperiplanar arrangement is now highly questionable. The
lack of stereoselectivity of 4 can be attributed to the absence of a
stereocenter at C-2 whereas, in our opinion, there are currently no
sound explanations for the low values of eudismic ratios for the
muscarone enantiomers.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
P.J. Carroll, M. De Amici, C. De Micheli, L. Toma
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