Absolute structure determination of the highly biologically active bisdehydrodoisynolic acids.
J Pharm Sci
; 89(4): 513-8, 2000 Apr.
Article
in En
| MEDLINE
| ID: mdl-10737912
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenanthrenes
Language:
En
Journal:
J Pharm Sci
Year:
2000
Document type:
Article
Affiliation country:
United States
Country of publication:
United States