Synthesis of key intermediates to 20(R)-and 20(S)-trifluoromethyl-23,24-dinor-25-hydroxy-cholesterol and VD3 analogs

Synthesis of 20(R)-and 20(S)-trifluoromethyl substituted steroids as the key intermediates (1a, 1b) to 23,24-dinor-20-trifluoromethyl-25-hydroxy-cholesterol and VD3 analogs, using trifluoromethyltrimethylsilane (CF₃SiMe₃) as a trifluoromethylating agent, was described.     

Synthesis and properties of trifluoromethylating steroid compounds

Trifluoromethyl steroids la,b; 2a,b; 3a,b have been synthesized by starting from estren 3,17-dicarbonyl-3,3-dimethyl ether (4) and dl-18-methyl-2(3)l5(10)-estra-diene-17-carbonyl-3-methyl ether (5),and by using trimthyltrifluoromethylsilane as the trifluoromethylating agent under the catalysis of tetrarnethylam-monium fluoride.The overall yields were 82%,76%; 54%,62%; and 27%,25%,respectively The α-configura tion of trifluoromethyl group of 17-position was determined by X-ray crystal diffraction method Compounds 1a,2a and 3a showed high affinity for rat uterus PRc.The test of biological activities of compounds 1b,2b and 3b is proceeding.