Anomalous oxidative cleavage of the side chain of 18-oxocortisol and its tetrahydro metabolite.
The course of oxidative side chain cleavage of two recently isolated 17 alpha-hydroxy C-18 oxygenated naturally-occurring corticosteroids differed in that 18-hydroxycortisol yielded a 17-ketosteroid (Chu M. D., and Ulick S. (1982) J. biol. Chem. 257, 2218-2224) whereas 18-oxocortisol yielded a gamma-etiolactone (Ulick S., Chu M. D. and Land M. (1983) J. biol. Chem. 258, 5498-5502). In an analytic application of the periodic acid oxidative cleavage reaction to 18-oxocortisol, the finding of a second product of the reaction prompted a reinvestigation of its course. Both the delta 4,3-ketone secreted form of the steroid and its tetrahydro urinary metabolite were cleaved predominantly to 17-ketosteroids along with smaller amounts of gamma-etiolactones, whose proof of structure is herein reported. This anomalous course of oxidative cleavage was considered to reflect an equilibrium between C-20 ketone and cyclic-hemiketal forms in which the glycerol-type side chain structure of the later becomes the precursor of a 17-ketosteroid. Because of the similarities between in vitro oxidative side chain cleavage and in vivo corticosteroid metabolism, these findings suggest that C-18 oxygenated steroids may contribute to the 17-ketosteroid fraction of human urine.
Chan
C K
CK
Veterans Administration Hospital, Bronx, NY 10468.
Ulick
S
S
D008401:Gas Chromatography-Mass Spectrometry; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000378:metabolism; D007664:Ketosteroids / Q000378:metabolism; D007783:Lactones / Q000378:metabolism; D010084:Oxidation-Reduction; D010504:Periodic Acid; D014297:Trimethylsilyl Compounds / Q000378:metabolism
D007664:Ketosteroids; D007783:Lactones; D014297:Trimethylsilyl Compounds; D010504:Periodic Acid; C038135:18-oxocortisol; D006854:Hydrocortisone