INVESTIGATIONS ON STEROIDS. XXIII. 6-HYDROXY DERIVATIVES OF 17α-HYDROXYPROGESTERONE AND REICHSTEIN'S COMPOUND S. STUDIES ON 6β, 11α-DIHYDROXYPROGESTERONE^*,¹

Abstract

The recent recognition that mammalian as well as microbial organisms possess enzyme systems capable of hydroxylating 3 -oxo-A4-unsaturated steroids at carbon atom 63 greatly stimulated the interest in 6-hydroxy derivatives of steroid hormones, first prepared by partial synthesis in this laboratory.The 6-acetoxy derivatives of such steroids as androstenedione, progesterone, and 11-desoxycorticosterone acetate were synthesized a number of years ago (2-4, cf. also 5). The correct assignment of steric configurations at carbon atom 6 of these compounds was made possible by a reinvestigation of the preparation of 6-acetoxy-ll-desoxycorticosterone acetate (6). It was established that treatment of a 3-oxo-5a-hydroxy-6/3-acetoxy steroid with dry hydrogen chloride in ethanol-free chloroform causes dehydration to the 3-oxo-6/3-acetoxy-A4unsaturated compound. If the reaction is carried out in the presence of a small amount of ethanol, as it is used as a stabilizer in commerical chloroform, the corresponding 6a-acetoxy compound results. The epimerization at carbon atom 6 is not coupled with the dehydration mechanism because the 3-oxo-6/3-acetoxy-A4-unsaturated steroid can be epimerized under these experimental conditions. The 6/3-acetoxy and 6a-acetoxy unsaturated steroids can be saponified to the 6/3-* This investigation was supported by research grants from: (a) the Rockefeller Foundation (Grant No. GA-NS 5134); (b) the National Cancer Institute (Grant No. CG-757-C2) of the National Institutes of Health, Public Health Service.1 A part of the findings of this paper (transformations leading to the 6/3-acetoxy derivative of Reichstein's compound S) was presented on July 22, 1952, at the 2nd International Congress of Biochemistry in Paris (cf. M. R. Ehrenstein, 6-Hydroxy Derivatives of Steroid Hormones. Their Stereochemistry and Possible Biochemical Significance, Symposium sur la Biochimie des Stéroides, p. 13, 11= Congrés International de Biochimie. Société d'Edition d'Enseignement Supérieur, Paris, 5®, 1952).2 Merck & Co. Predoctoral Fellow (1951. This paper is based on a section of a thesis submitted by Klaus Georg Florey to the Graduate School of Arts and Sciences of the University of Pennsylvania in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Physiological Chemistry (June 1954). 3 Cf. e.g. the review article, Hydroxylierungen von Steroiden durch biologische Methoden(1).1331 Philadelphia 4, Penn a.