Triterpene Carboxylic Acids as Cortisol Lowering Agents and Synthesis of Hexadeuterated Beta-Ionone

Abstract

In part one, betulinic acid (1) was isolated from the American Sycamore (Platanus occidentalis) in 1.6% yield, while ursolic acid (3) was isolated from Fuji and McIntosh apple peels in 1.0% and 0.8% crude yields, respectively. Oleanolic (4) and dehydrocanophyllic (6) acids were previously available, along with several analogs. Additional analogs of 1, 3 and 4 were prepared, including 9 new compounds, for a total of 51 compounds. Compounds were initially screened for cortisol lowering properties in vitro using a fish head kidney cell assay. Platanic acid (43) was selected for in vivo study in rats, along with 1 and a blend of Platanus occidentalis and Souroubea sympetela. No significant cortisol lowering was observed in vivo. In part two, β-ionone-d6 (75) was synthesized in 6.5% yield from ethyl 2-oxo-cyclohexane carboxylate (77). Total deuterium incorporation was 99.85%, with 0.03% d0 analog. 75 was converted to retinoic acid-d6 (93) in 2.2% yield.