RESEARCH TWO ROUTES TO NEW STEROIDS
7 cr-HYDROXYSTEROIDS
CH 2 OH
VIA MERCK (Microbial)
VIA SCHERING (Chemical)
6—DEHYDROPREDNISONE (with bond s h o w n in gray) 6—DEHYDROCORTISONE (without bond s h o w n in gray)
Molds, Chemical Yield N e w Steroids N o w 7a- and 7j3-hydroxysteroids are a v a i l a b l e via new Merck and Schering techniques X w o N E W TECHNIQUES for modifying
the steroid nucleus to increase pharma cological activity introduce hydroxyl groups at carbon 7. The results are a host of new compounds—lot- and 7βhydroxysteroids. Major potential uses for them now being clinically explored: • Antiarthritic agents. • Antitumor agents ( cancer therapy ). • Anesthetics. Merck Sharpe & Dohme has come up with one technique—a microbiologi cal method to introduce both 7 a- and 7/3-hydroxyls into the Β ring of various 54
C&EN
MARCH
3 1 . 1958
steroidal compounds. Not only is this a "first" for /?-hydro:xysteroids. but it presents a simple "bathtub" technique to synthesize this series of potentially pharmacologically active steroids, Merck's William J.VIcAleer told ACS members at the recent N e w York Meeting-in-Miniature. Using a chemi cal route, Schering scientists sxicceeded in making Ta-hydroxysteroids. Both groups presented papers on their work. Basically, the YIerok method consists of adding the steroid substrate to a vat of fermenting organisms, then extract ing b y classical isolation techniques. The more rapidly oxidized 7cK-hydroxy
epimer (axial) is produced by a species of Helminthosporium, while the Ίβhydroxy epimer (equatorial) is formed by incubation with a Cladiosporium culture. So far, such substrates as progesterone, desoxycorticosterone, Reichstein's substance S ( 4-pregnene17a:, 21-diol-3, 20-dione), and cortisone all have been converted to their 7-hydroxy derivatives by these cultures. And yields are good, too, ranging from 30 to 50'Κ says McAleer. Schering's method utilizes the newly available 6-dehydrosteroids, such as 6-dehydroprednisone (C&EN, Sept. 16, 1957, page 6 6 ) . Peroxidation of this compound, followed by epoxide-ring opening with hydrogen bromide and debrominating the bromohydrin, yields 7a-hydroxyprednisone. And Schering has extended this method to preparing 7c*-hydroxycortisone. too, says Alex L. Nussbaimi.
