Microbiological Transformations of Steroids. V. The Oxygenation of 17α-Hydroxyprogesterone to 6β,17α-Dihydroxyprogesterone and 11α,17α-Dihydroxyprogesterone¹

Abstract

Incubation of 17a-hydroxyprogesterone with Rhizopus arrhizus Fischer (A.T.C.C. 11145) produced in good yield 6&17adihydroxyprogesterone and in small amounts 1 I ~~~17a-dihydroxyprogesterone. Incubation with Rhizopiis nigricans Ehrh (.4 T C.C R22711) gave excellent yield4 of I 1 ol,17a-dihydrozyprogesterone and very little of 6@,17a-dihydroxyprogesterone DiscussionIn paper 111 of this series? we reported that Rhizopus arrhizus oxygenates desoxycorticosterone in good yield to 6P-hydroxy-1 l-desoxycorticosterone and produces only very small amounts of 11epicorticosterone.Incubation of desoxycorticosterone with Rhizopus nigricans gave 1 1-epicorticosterone in good yield.When the bioconversion of Reichstein's Compound S was investigated'" essentially the same results were obtained] inasmuch as 6i3117a,21-trihydroxy-.l-pregnene-3,20-dione and 1 laIl7a,21-trihydroxy-4-pregnene-3,20-dione (compound 11-epi F) were produced by Rhizopus arrhizus as well as by Rhizopus nigricans. In conformity with the previous experience Rhizopus nigricans performed 11oxygenation in higher yields than Rhizoeus arrhizus did. These results pointed to a significant difference between the oxygenation of progesterone in the one case and of desoxycorticosterone and Iieichstein's Compound S in the other. The introduction of one or more hydroxy groups into the side chain of the basic substrate molecule, Le., proges-

Partition Chromatography Of Steroids

“…Microbiological transformations of steroids are of considerable importance. Much of this work has been carried out by Peterson (306) and his associates, who used partition chromatography routinely in production control (308,212,304,97,98,309,261,126,307,262,310,127,156,263,269,459,285).8…”

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

“…As has been shown by investigators of the Research Laboratories of the Upjohn Company (14), fermentation of 17a-hydroxyprogesterone by either of the microorganisms Rhizopus nigricans or Rhizopus arrhizus yields lla,17a-dihydroxyprogesterone and a second compound to which the structure of 68, 17a-dihydroxyprogesterone (A4-pregnene-6/3,17 a-diol-3,20-dione) (VIII) had been tentatively assigned. Comparison of the characteristics of the latter biosynthetic product and of its diacetate with those of the synthetic VIII4 and XHI (cf.…”

Hydroxylation of Progesterone and 11-Desoxy-17-Hydroxycorticosterone by Aspergillus and Penicillium

“…demonstrated by the Upjohn group that an oxygen function at carbon-11 can be introduced microbiologically by members of the Mucorales (Eppstein et al, 1953a;Eppstein et al, 1953b;Meister et al, 1953aMeister et al, , 1953bMurray and Peterson, 1952;Peterson et al, 1953a;Peterson et al, 1953b), by species of Penicillium (Murray and Peterson, 1953a) and by species of Aspergillus (Murray ). Fried et al (1952) have also demonstrated that Aspergillus niger introduces a hydroxyl with the alpha configuration at carbon-11 of progesterone, 17a-hydroxyprogesterone and 11-desoxy-17-hydroxycorticosterone (Reichstein's substance S).…”