Ring D oxygenated Spirolactones. Characterization of human metabolic product of spironolactone

15alpha-Hydroxycanrenone (1b) was prepared from canrenone (1a) by microbiological oxidation with a penicillium species. The product was identical with one obtained from the metabolism of spironolactone(3) in human. Oxidation of 1b with Jones regent furnished the corresponding 15-oxocanrenone (1d) which underwent base-catalyzed beta elimination to generate an alpha,beta-unsaturated cyclopentenone system. 15alpha-Hydroxycanrenone (1b) failed to show antimineralocorticoid activity at the screening dose of 2.4 mg while the oxo derivative 1d exhibited approximately 15% the activity of 3. Since the activity of canrenone is 38% that of spironolactone, introduction of the carbonyl group at the 15 position of canrenone resulted in a reduction in activity. This effect is opposite to that observed with 6-dehydroprogesterone.