Synthesis of 16 alpha-hydroxyandrost-4-ene-3,17,19-trione and 3 beta, 16 alpha-dihydroxyandrost-5-ene-17,19-dione; potential intermediates of estriol biosynthesis.
16 alpha-Hydroxyandrost-4-ene-3,17,19-trione (10) was synthesized from the 16 alpha-hydroxy-6 beta,19-epoxy-17-one 3 via protection of the 16 alpha-hydroxy function as its tert-butyldimethylsilyl ether or acetate. Reductive cleavage of the epoxy ring of the silyl ether 4 or the acetate 5 with zinc dust gave the 19-alcohol 6 or 7, which was treated with pyridinium dichromate or Jones reagent, respectively, and then hydrolyzed with diluted sulfuric acid, yielding the desired steroid 10. 3 beta,16 alpha-Dihydroxyandrost-5-ene-17,19-dione (14) was also synthesized from 5 alpha-bromo-3 beta,16 alpha-diacetoxy-6 beta, 19-epoxyandrostan-17-one (11) through the intermediates 12 and 13 with the 3 beta- and 16 alpha-hydroxy functions protected as their acetates in a reaction sequence similar to that above.
Numazawa
M
M
Tohoku College of Pharmacy, Sendai, Japan.
Hoshi
K
K
Konno
T
T
Nagaoka
M
M
D000734:Androstenediols; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D004964:Estriol / Q000096:biosynthesis*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis*
D000734:Androstenediols; D013438:Sulfhydryl Compounds; C065505:16-hydroxy-19-oxo-4-androsten-3,17-dione; C066747:3,16-dihydroxyandrost-5-ene-17,19-dione; D000735:Androstenedione; C041676:2-(N-decylamino)-ethanethiol; D004964:Estriol