Synthesis and Biological Activity of (22E, 24R)- and (22E, 24S)-1α, 24-Dihydroxy-22-dehydrovitamin D_3

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Chemical synthesis of (22E, 24R)- and (22E, 24S)-1,24-dihydroxy-Δ^<22>-vitamin D_3 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 Δ^7 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 D_3 compound bound equally well to the chick intestinal cytosol receptor as 1,25-dihydroxyvitamin D_3,while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than 1,25-dihydroxyvitamin D_3 ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of 1,25-dihydroxyvitamin D_3.
社団法人日本薬学会の論文
1984-10-25