Synthesis and Biological Evaluation of (23R)- and (23S)-24,24-Difluoro-1α, 23,25-trihydroxyvitamin D_3

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The syntheses and biological evaluations of (23R)- and (23S)-24,24-difluoro-1α, 23,25-trithydroxyvitamin D_3 (3a and 3b), new C-24 fluorinated analogs of 1α, 25-dihydroxyvitamin D_3,are described. The syntheses of these compounds were achieved in 3 steps from (5Z, 7E, 20R)-1α, 3β-bis-[(tert-butyldimethylsilyl)oxy]-20-formylmethyl-9,10-seco-5,7,10(19)oregnatriene (5) which is derived from vitamin D_2. The absolute configuration at the C-23 position of 3a and 3b was determined by the modified Mosher method. The relative affinities of 3a and 3b to the vitamin D receptor were both 10 and 14 times lower than that of 1α, 25-dihydroxyvitamin D_3 (1), and to vitamin D binding protein were also both 130 and 40 times lower. The HL-60 cell differentiating activity of 3a was 6 times more potent than that of 1,while there was no remarkable difference in activity between 3b and 1.
1998-12-15