15-BETA-HYDROXYSTEROIDS .2. STEROIDS OF THE HUMAN PERINATAL-PERIOD - THE SYNTHESIS OF 3-ALPHA,15-BETA, 17-ALPHA-TRIHYDROXY-5-BETA-PREGNAN-20-ONE

Steroids hydroxylated at C-15 have long provided useful information ab out the well-being of the fetus and Seto-placental unit in human pregn ancy. In an attempt to develop a new and reliable immunoassay method f or use in newborn screening programs for congenital adrenal hyperplasi a, we report the chemical synthesis of 3 alpha, 15 beta, 17 alpha-trih ydroxy-5 beta-pregnan-20-one (2) from 3 alpha-hydroxy-5 beta-androstan -17-one (4) in 9 steps. In brief 3 alpha-hydroxy-5 beta-androst-15-en- 17-one (6), was obtained from 4 by phenylselenation yielding 3 alpha-h ydroxy-16 alpha-phenylseleno-5 beta-androstan-17-one (5a) which on deh ydroselenation gave 6. Introduction of the 15 beta-hydroxy group and t he side-chain was achieved by the addition of 2-lithio-2-methyl-1,3-di thiane followed by an acid-catalyzed rearrangement to give 20,20-trime thylenedithio-5 beta-pregn-16-en-3 alpha,15 beta-diol (8a). Acetylatio n then cleavage of the dithioacetal gave 3 alpha, 15 beta-diacetoxy-5 beta-pregn-16-en-20-one (9) which on hydrogenation gave 3 alpha, 15 be ta-diacetoxy-5 beta-pregnan-20-one (10). Reaction of base and oxygenat ion of 10 gave a mixture of products which on basic hydrolysis gave 3 alpha, 15 beta, 17 alpha-trihydroxy-5 beta-pregnan-20-one (2) in an ov erall yield of 8.8%.