15-BETA-HYDROXYSTEROIDS .4. STEROIDS OF THE HUMAN PERINATAL-PERIOD - THE SYNTHESIS OF 3-ALPHA,15-BETA, 17-ALPHA-TRIHYDROXY-5-ALPHA-PREGNAN-20-ONE AND ITS A B-RING CONFIGURATIONAL ISOMERS/

In recent years several 15 beta-hydroxysteroids have emerged pathognom onic of adrenal disorders in human neonates of which 3 alpha,15 beta,1 7 alpha-trihydroxy-5 beta-pregnan-20-on (2) was the first to be identi fied in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the thre e remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydr oxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 a lpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta- pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydro xy-5-pregnen-20-one (11), a product of chemical synthesis was converte d to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydr oxy-4-pregnen-3,20-dione (4), a product of microbiological transformat ion, resulted in the preparation of 8. In brief, selective acetate hyd rolysis of 11 gave 15 beta-acetoxy-3 beta, 17 alpha-dihydroxy-5-pregne n-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta, 17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermed iate for the synthesis of the 3 beta(and alpha), 5 alpha-isomers. Hydr olysis of the 15 beta-acetate gave 7, whereas oxidation with pyridiniu m chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan -3,20-dione (14) which on reduction with L-Selectride and hydrolysis o f the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta ,17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.