THE SYNTHESES OF 3-SUBSTITUTED PERFLUOROALKYL STEROIDS

The syntheses of three classes of C-3 perfluoroalkyl substituted stero ids are described. They are the 3 beta-hydroxy-3 alpha-perfluoroalkyla ndrost-4-en-17-ones (5a-c), 3-perfluoroalkylandrosta-3, 5-dien-3-ones (8a-c) and 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-5-en-17-ones ( 12a-c). Addition of a series of perfluroalkylorganometallic reagents ( R(F)Li; R(F) = C2F5, C3F7, or C4F9) to the 3 position of silylated tes tosterone 2b afforded Delta(4)perfluoroalkyl carbinols 3. In Scheme I, deprotection with HF and oxidation at the C-17 carbon with PCC produc ed Delta(4) ketones 5. In Scheme 2 dehydration of 3 with 1,2-phenylene phosphorochloridite and iodine afforded Delta(3,5) dienes 6 which were deprotected and oxidized as above to the C-17 ketones 8. In Scheme 3 isomerization of the double bond of 3 from the C-4 to the C-5 position using the allylic halogenation followed by treatment with lithium alu minum hydride led to the synthesis of the double bond isomer series 12 . A new method for dehydration was developed On average and within exp erimental error, 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-5-en-17 ones (12a-c) were better than the 3-perfluoroalkylandrosta-3,5-dien-17 -ones (8a-c) and 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-4-en-17- ones (5a-c) at inhibiting glucose-6-phosphate dehydrogenase.