Design and Synthesis of a 1α,25-Dihydroxyvitamin D3 Dimer as a Potential Chemical Inducer of Vitamin D Receptor Dimerization

A dimer comprising two 1α,25-dihydroxyvitamin D3 units linked by an alkyl side chain at C-11 was synthesized with a view to the simultaneous binding of two vitamin D receptor (VDR) molecules and the consequent induction of VDR dimerization. The short, convergent synthesis uses a stereoselective cuprate addition to introduce the linking side chain and a key ruthenium olefin metathesis as the dimerization step.