Synthesis, conformational analysis, and biological evaluation of 19-nor-vitamin D3 analogues with A-ring modifications.

We have synthesized several isomers of 19-nor-vitamin D analogues possessing a hydroxy group at C-2 as well as novel derivatives bearing an epoxy substituent at the A-ring. All vitamins were prepared in convergent syntheses utilizing the modified Julia olefination. 1alpha,2alpha,25-Trihydroxy-19-nor-vitamin D(3) (3) and 2beta,3beta-epoxy-1alpha,25-dihydroxy-3-deoxy-19-nor-vitamin D(3) (10), which showed the highest affinity to the vitamin D receptor, displayed the highest potency among the tested compounds to inhibit the proliferation of MCF-7 breast cancer cells.