Synthesis and biological activities of 26-hydroxy-27-nor-derivatives of 1α,25-dihydroxyvitamin D3

Article abstract of DOI:10.1016/S0039-128X(96)00120-1

Starting with (20S)-20-(p-toluenesulfonyl)oxymethyl-pregna-1,5-dien-3- α-ol (4), we synthesized three vitamin D analogs in 10 to 11 steps: 1α,26- dihydroxy-27-nor-vitamin D₃ (1), its 3-epi analog (2), and 2β-methoxy- 1α,26-dihydroxy-27-nor-vitamin D₃ (3). We tested the derivatives in the murine mesenchymal cell line C3H10T 1/4 . All substances were less potent in inhibition of cell proliferation, inhibition of adipocyte differentiation, and induction of gene activation, and had a lower affinity to the vitamin D receptor than the native vitamin D₃ metabolite 1,25(OH)₂D₃. The affinity of 1 to the vitamin D binding protein was about three times higher than that of 1,25(OH)₂D₃.