The first synthesis and biological testing of the enantiomer of 1 alpha,25-dihydroxyvitamin D-3

The 1 alpha ,25-dihydroxyvitamin D-3 enantiomer was synthesized and examine d in biological tests. The ring A precursor was prepared from vitamin D-2 e mploying the Mitsunobu reaction for inversion of the configuration at C-3 a nd SeO2 hydroxylation at C-l. The CD rings-side chain portion was synthesiz ed from an optically active hexanoic acid derivative using diastereoselecti ve tandem Mukaiyama-Michael addition and vinylsulfone reduction as the key steps. The ring A and CD rings building blocks were combined using the Juli a alkenylation reaction. 1 alpha ,25-Dihydroxyvitamin D-3 enantiomer shows no significant affinity to the vitamin D receptor. (C) 2001 Elsevier Scienc e Ltd. All rights reserved.