SUMMARY 1. Four new metabolites of adrenal hormones have been isolated from human urine after ACTH administration and identified by isotopic dilution after a tracer dose of hydrocortisone-4-C14. The compounds obtained were (1) pregnane3ar,llp, 17o(,20a,21-pentol; (2) 3a, 1701,20a,21-tetra- hydroxypregnane-11-one; (3) pregnane-3a!, lip ,17a ,208,21-pentol; (4) 3ar, 17~~) 2Op ,21-tetrahydroxypregnane-1 l-one. Trivial names were sug- gested for these products. 2. On the basis of the isotopic dilution studies it was estimated that these compounds represent a minimum of 30 per cent of the metabolites of hydrocortisone found in the neutral ether-soluble extract of human urine after hydrolysis of their conjugates by means of beef liver @-glu- curonidase. 3. 3a, 17ar ,2Oa!, 21-Tetrahydroxypregnane-11-one was isolated from human urine after administration of 100 mg. of cortisone-t by vein. It was estimated that the metabolite represented about 6 per cent of radio- activity in the neutral ether-soluble fraction after hydrolysis by means of beef liver p-glucuronidase. 4. A novel and efficient synthesis for 3a, 17a,20a,21-tetrahydroxy- pregnane-11-one was described. The procedure is based upon the solvoly- sis of 3~r, 17a( ,21-triacetoxy-20P-p-toluenesulfonoxypregnane-ll-one with aqueous acetic acid in the presence of potassium acetate. The reaction is an example of “neighboring group effect ” in an acetyl migration with inversion of configuration. 5. The preparation of the related compounds, 3a,21-diacetoxy-17a-hy- droxy-20P-p-toluenesulfonoxypregnane-11-one, 3a,21-diacetoxy-17~u, ~OLU- epoxypregnane-11-one, and pregnane-3oL, llfl ,17ar ,2Oa! ,21 -pentol has been described. The authors express their gratitude to their colleagues Dr. Leon Hellman and Dr. Olaf Pearson for their cooperation in the studies with patients. We are especially indebted to Evelyn Meyer for technical assistance and to Friederike Herling for her valuable contributions to the interpretation of the infra-red spectra.
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