The synthesis of p-hydroxyphenyl-alkylated-cyclohexenecarboxylic acids continues, and the multitude of diastereomers are being isolated and resolved into their R and S enantiomers. Their activity as anti-prostate cancer agents and in prostate enlargement therapy continues, based on our findings that (+)-Z-bisdehydrodoisynolic acid is a very active therapeutic agent for prostate disease. Our recent research showed that reactions involving rotationally restricted, sterically hindered cations, radicals and anions proceed largely if not exclusively via inversion, often providing a different conformation. We are now exploring the possibility that the pKa of such compounds, whose deprotonation-reprotonation traverses such anions, will be quite different from their non-hindered, non-rotationally restricted counterparts, and will require a new set of "substituent sigma constants"to evaluate their effect on the acidity. We have shown that a number of compounds containing an OH group crystallize from a solvent into crystals whose X-ray structures show are composed of intermolecularly H-bonded structures. These crystals melt on heating, but when the melt is cooled it does not crystallize again. In CDCl3, the NMR of the melt is identical to that of the crystals. It is possible that in the melt, the molecules move around each other and do not readily interact in a conformation thermodynamically conducive to intermolecular H-bond ing, hence do not form crystals. We are studying this phenomenon in a variety of types of compounds.

Meyers, C.Y.; Chan-Yu-King, R.; Hua, D.H.; Kolb, V.M.; Matthews, W.S.; Parady, T.E.; Horii, T.; Sandrock,, P.B.; Hou,; Y.; Xie, S. and Robinson, P.D. Unexpected Differences in the a-Halogenation and Related Reac- tivity of Sulfones with Perhaloalkanes in KOH-t-BuOH. J. Org. Chem. 2003, 68, 500-511.

Xie, S., Yuqing Hou, Y., Meyers, C. Y. and Robinson, P. D. Lactone precursors of prostate therapy agents. I. (±)-anti-7-Ethyl-1-(4-methoxyphenyl)-5,5,syn-8-trimethyl-2-oxabicyclo[2.2.2]octan-3-one, a bicyclic d-lactone. Acta Crystallogr. 2003, E59, o-403-o-405.

Xie, S., Yuqing Hou, Y., Meyers, C. Y. and Robinson, P. D. Lactone precursors of prostate therapy agents.II. (±)-5-Ethyl-endo-4-(4-methoxyphenyl)-2,2,anti-8-trimethyl-6-oxabicyclo[3.2.1]octan-7-one, a bicyclic g-lactone Acta Crystallog. 2003, E59, o-406-o-407.

Wilson, T.; March, H.; Banz, W. J.; Hou, Y.; Adler, S.; Meyers, C. Y.; Winters, T. A.; Maher, M. A. Antioxidant Effects of Phyto- and Synthetic Estrogens on Cupric-Ion Induced Oxidation of Human Low-Density Lipoproteins In Vitro. Life Sciences, 2002, 70, 2287-2298.

Xie, S.; Hou, Y.; Meyers, C. Y.; Robinson, P.D. Cis-2-methyl-trans-3-ethyl-6,6-dimethyl-4-ketocyclohexanecarboxylic Acid. An Intermediate in the Synthesis of a Highly Potent Estrogen. Acta Crystallogr. 2002, C58, o159-o161.

Chan-Yu-King, R., Anil, J., Meyers, C. Y. and Robinson, P. D. Dichloromethyl Phenyl Sulfone. Acta Crystallogr., 2002, E58, 592-595.

Meyers, C. Y., Hou, Y., Winters, T. A., Banz, W. J. and Adler, S. Activities of a Non-classical Estrogen, Z-Bis-dehydrodoisynolic Acid, with ERa and ERb. J. Steroid Biochem. Mol. Biol., 2002, 82, 33-44.

Kolb, V. M., Donahue, M. G. Putnam, E. A., Meyers, C. Y. and Robinson, P. D. Cyclopropyl m-Nitrophenyl Ketone, Acta Crystallogr. 2002, E58, o-1161-o-1163.