Chemical methods for the conversion of Prednisolone to 11-β-hydroxy-1,4-androstadiene-3,17-dione

Abstract

Several microbial transformations of steroids to 17-keto cortisones through side chain cleavage have been presented in the literature; however, yields and product selectivity in these methods were low. In the present study, some new methods have been identified for the side chain cleavage of prednisolone (1) to form 11- β-hydroxy-1,4-androstadiene-3,17-dione (11- β-hydroxy ADD). Prednisolone upon reaction with zinc chloride in dry THF results in the formation of cleavage product in good yield (76%). 11- β-hydroxy ADD (2) has been formed in moderate yield (60%) under the Reformatsky reaction conditions by reacting with zincate. While performing the Wittig reaction using stable ylides, again results in the formation of compound 2 in good yield (56%). Side chain cleavage of prednisolone was confirmed from the physical and analytical data and similar when compared with the literature reports. A few chemical methods were investigated for the side chain cleavage of prednisolone in order to obtain 11-β-hydroxy-1,4-androstadiene-3,17-dione. Among these methods, ZnCl2 mediated transformation gives the best results with 76% yield.