124 Perspectives in Microbiology 



HO 



HO H 



X XV 



Desoxycholic Acid Epihydrocortisone 



of the drug to the patient was prohibitive and cheaper 

 methods for its synthesis were imperative. 



The basic structural requirements of steroids necessary 

 for the biological responses observed clinically in rheuma- 

 toid arthritis to date are found only in cortisone (VIII) 

 and hydrocortisone (IX) or their derivatives. 



In view of the many complex chemical reactions per- 

 formed by microorganisms, it was hoped that a microbio- 

 logical approach might lead to a simpler method. Such a 

 method might introduce oxygen into the critical 11 -posi- 

 tion of readily available steroids to produce cortisone 

 (VIII) and hydrocortisone (IX) directly or to produce 

 II -oxygenated intermediates which could then be readily 

 converted to these important compounds (VIII and IX) 

 by chemical methods. 



The microbiological oxygenation of steroids at nuclear 

 positions other than 7 was first reported from our labora- 

 ties (29) in 1952. That report outlined a one-step method 

 for the introduction of oxygen into the strategic carbon 

 1 1 position by fungi of the order Mucorales, and more spe- 

 cifically, described the bioconversion of progesterone (XI) 

 to a new compound lla-hydroxyprogesterone (XII). Con- 

 firmation of this work was obtained by Mancera et al. (15) 

 and by Kahnt et al. (11). Fried and co-workers (5) inde- 

 pendently reported 11 -oxygenation of steroids by an 

 Aspergillus (Wisconsin strain) (21, 23). Colingsworth et al. 

 (1, 7) showed that Reichstein's compound S (XIII) could 

 be converted to hydrocortisone by Streptomyces fradiae. 

 Further confirmation of this type of transformation was ob- 



