The synthesis of A- and B-ring fluorinated analogues of cholesterol

The synthesis of a number of mono- and difluorinated steroids with the pote ntial to act as probes of the metabolism of cholesterol is described. 2 alp ha-Fluorocholestan-3-one 7, 4-fluorocholest-5-en-3-one 11 and 6-fluorochole st-4-en-3-one 12 were synthesised from the appropriate silyl enol ethers us ing 1-fluoropyridinium triflate, and subsequently reduced to the correspond ing alcohols, 8, 13 and 14 respectively. A similar approach was used to syn thesise 2,2-difluorocholestan-3-ol 16 starring from the monofluoro steroid 7. To synthesise 4,4-difluorocholestan-3 beta-ol 26, 3 beta-acetoxycholesta n-4-one 25 was generated via an acid catalysed rearrangement of 4,5-epoxych olestan-3-one 20 and treated with DAST. Finally, a difluorocyclopropyl anal ogue of Cholesterol 28 was synthesised using chlorodifluoroacetic acid.