ChemInform Abstract: Design and Synthesis of 1α,25-Dihydroxyvitamin D3 Analogues with Fixed Torsion Angle C(16-17-20-22)

A series of semi-rigid analogues of the hormone 1α,25-dihydroxyvitamin D3 have been designed in order to study the topology required for binding to the hormone receptor (VDR). The new vitamin D3 analogues 2-5 possess a rigid C17-C20 bond and minimal structural modifications on the side-chain with respect to the hormone. Key steps for the introduction of the side-chains of the new analogues 2-5 from hydrindanone 6 involve a stereoselective Wittig reaction, olefin isomerization and dihalocyclopropanation.