Synthesis of 17β-[(1S)-1-hydroxy-2-propynyl]- and 17β-[(1R)-1-hydroxy-2-propynyl]androst-4--en-3-one. Potential suicide substrates of 20α- and 20β- hydroxysteroid dehydrogenases

The title compounds have been synthesized for evaluation as potential suicide substrates of 20α and 20β hydroxysterold dehydrogenases. Synthesis was achieved by the following route. Acetylenedimagnesium bromide was reacted with 3β-hydroxyandrost-4-ene-17β-carboxaldehyde to give 17β-[ (1R,S)-1-hydroxy-2-propynyl] androst-4-en-3β-ol. Separation of the R and S diols was achieved by HPLC (high pressure liquid chromatography). Selective oxidation of the 3β-hydroxyl group with Jones reagent at 0° gave the title compounds. Further oxidation with Jones reagent converted each acetylenic alcohol to the conjugated acetylenic ketone, 17β-(1-oxo-2-propynyl)androst-4-en-3-one.