Synthesis and Biological Evaluation of 1α,25-Dihydroxyvitamin D3Analogues with a Long Side Chain at C12 and Short C17 Side Chains Academic Article uri icon


  • Structure-guided optimization was used to design new analogues of 1α,25-dihydroxyvitamin D₃ bearing the main side chain at C12 and a shorter second hydroxylated chain at C17. The new compounds 5a-c were efficiently synthesized from ketone 9 (which is readily accessible from the Inhoffen-Lythgoe diol) with overall yields of 15%, 6%, and 3% for 5a, 5b, and 5c, respectively. The triene system was introduced by the Pd-catalyzed tandem cyclization-Suzuki coupling method. The new analogues were assayed against human colon and breast cancer cell lines and in mice. All new vitamin D₃ analogues bound less strongly to the VDR than 1α,25-dihydroxyvitamin D₃ but had similar antiproliferative, pro-differentiating, and transcriptional activity as the native hormone. In vivo, the three analogues had markedly low calcemic effects.


  • Alvarez Diaz, Silvia
  • Carballa, Diego M
  • Seoane, Samuel
  • Zacconi, Flavia
  • Pérez, Xenxo
  • Rumbo, Antonio
  • Alvarez-Díaz, Silvia
  • Larriba, María Jesús
  • Pérez-Fernández, Román
  • Muñoz, Alberto
  • Maestro, Miguel
  • Mouriño, Antonio
  • Torneiro, Mercedes

publication date

  • October 25, 2012