Absolute Structure Determination of the Highly Biologically Active Bisdehydrodoisynolic Acids

(+)-Z-Bisdehydrodoisynolic Acid Enhances Basal Metabolism and Fatty Acid Oxidation in Female Obese Zucker Rats

“…In this study, we confirmed earlier findings [4–6] that (+)- Z -BDDA reduced weight gain, independently of energy intake. Similarly, female Zucker diabetic fatty (ZDF) rats administered (+)- Z -BDDA for six months had lower body weight, total adiposity, and enhanced physiological and cardiovascular function [4].…”

“…Based on the structural similarity to 17 β -estradiol, DAs were originally investigated as an alternative to hormone replacement therapy [2, 3]. More recently, we demonstrated that administration of these estrogenic compounds suppressed weight gain in normal weight and obese rodents [4–6]. In particular, IP injection of various BDDA isoforms lowered body weight and total adiposity in Wistar and Sprague-Dawley rats, independently of gender or energy intake [5].…”

(+)‐Z‐Bisdehydrodoisynolic Acid Ameliorates Obesity and the Metabolic Syndrome in Female ZDF Rats

“…Bisdehydrodoisynolic acid (BDDA), 1 along with other doisynolic acids, are estrogenic compounds originally obtained from alkali fusion of estrone and equilenin (1). These secosteroids and a number of related pseudoseco‐steroid acids exhibit estrogenic and antiestrogenic activities depending on dosage (2, 3, 4, 5, 6) and, thus, may be considered selective estrogen receptor (ER) modulators (SERMs). Assays of (±)‐ Z ‐BDDA for estrogenicity have revealed a high estrogenic potency of this compound (2, 3, 4, 5, 6).…”

“…Recently, we have also demonstrated that an activity‐binding paradox, exhibited with (+)‐, (−)‐, and (±)‐ Z‐ BDDA and ERα, is also associated with ERβ (2). Moreover, the failure of ERβ to explain the activity‐binding paradox emphasizes the need for additional in vivo metabolic and pharmacokinetic studies and continued consideration of alternative mechanisms and/or receptors (2, 3, 4, 5).…”

trans-3-Ethyl-cis-2,6,6-trimethyl-4-oxocyclohexanecarboxylic acid: an intermediate in the synthesis of a highly potent estrogen

“…Although they showed these compounds to be uterotropically potent, they presumed them to possess high estrogen-receptor binding af®nity as well, but they did not test this property. In contrast, our more recent studies of estrogenic carboxylic acids have revealed that they exhibit the paradox of high uterotropic activity with very poor binding af®nity for estrogen receptors (Meyers et al, 1988(Meyers et al, , 1997(Meyers et al, , 2000Banz et al, 1998;Robinson et al, 1999;Hou & Meyers, 2000), hence our interest in preparing the Crenshaw compounds, unequivocally determining their structures and correlating them with their uterotropic activities and estrogen-receptor binding af®nities.…”