Absolute structure determination of the highly biologically active bisdehydrodoisynolic acids.
In a project designed to relate the unexpected in vivo and in vitro properties exhibited by (+)- and (-)-bisdehydrodoisynolic acid with their absolute stereochemical structure, an X-ray crystal-structure analysis was undertaken of the highly estrogenic, poorly binding (-) enantiomer. (1) and (13)C NMR spectra are also reported for the first time. The crystal structure shows the cis juxtaposition of the carboxyl and ethyl groups, which are separated by a large torsion angle, and that only the carbon atom holding the carboxyl group is out of the plane in which the remainder of the fused three-ring moiety lies. The crystal structure, which unequivocally characterizes the (-) enantiomer as cis-13(S),14(R) and, implicitly, the (+) enantiomer as cis-13(R),14(S), will be useful in continued studies aimed at explaining the selective estrogen receptor modulation (SERM) of these enantiomers which, in some cases, produces significantly different end-organ effects compared to those of estradiol, in both males and females, affording the promise of a variety of therapeutic and pharmacologic applications.
Meyers
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CY
Department of Chemistry and Biochemistry-4409, Southern Illinois University, Carbondale, Illinois 62901, USA. cal@chem.siu.edu
Hou
Y
Y
Robinson
P D
PD
Adler
S
S
Banz
W J
WJ
Winters
T A
TA
D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010616:Phenanthrenes / Q000737:chemistry*
D010616:Phenanthrenes; C118032:bisdehydrodoisynolic acid