Synthesis and Biological Activity of (22E, 24R)- and (22E, 24S)-1α, 24-Dihydroxy-22-dehydrovitamin D₃

抄録

Chemical synthesis of (22E, 24R)- and (22E, 24S)-1, 24-dihydroxy-Δ²²-vitamin D₃ has been achieved starting with the commercially available dinorcholenic acid acetate. Synthesis involved introduction of the 1-hydroxy group by a reduction of the 1, 2-epoxide generated by epoxidation of the 1, 4, 6-trien-3-one. The side chain on the steroid was then constructed by means of a Wittig reaction followed by introduction of the Δ⁷ bond by standard methods and its protection with 1-phenyl-1, 2, 4-triazoline-3, 5-dione. Subsequent reduction of the hydroxy groups in the steroid side chain followed by reduction of the Diels-Alder addition products yielded the both 24-isomers. The 5, 7-dienes were irradiated and the corresponding vitamin D compounds isolated. Nuclear magnetic resonance was used to identify individual isomers. The (22E, 24S)-1, 24-hydroxyvitamin D₃ compound bound equally well to the chick intestinal cytosol receptor as 1, 25-dihydroxyvitamin D₃, while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than 1, 25-dihydroxyvitamin D₃ ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of 1, 25-dihydroxyvitamin D₃.