Synthesis of a novel analog of the C,D ring and side chain of 1α, 25-dihydroxyvitamin D3

ORGN 189

Joanna L. S. Turteltaub, and Paul G Williard. Department of Chemistry, Brown University, 324 Brook Street, Providence, RI 02912
Cellular processes associated with 1α, 25-dihydroxyvitamin D3, [1α, 25(OH)2D3], include immuno-suppression, antiproliferative and differentiation induced activity and skeletal development and calcium homeostasis. Vitamin D and its metabolites have become therapeutic agents for the treatment of numerous diseases including osteoporosis, autoimmune diseases, psoriasis, cancer and leukemia. However, therapeutically useful doses of 1α, 25(OH)2D3 produce sever hypercalcemia. A novel analog of the C, D ring and side chain of Vitamin D3 incorporating 16-ene, 20-cyclopropyl and 24-oxo moieties has been synthesized. It is anticipated that the structural motifs of this compound will enhance antiproliferative and differentiation induced activities while decreasing the toxic effect of hypercalcemia.