Jp. Sestelo et al., Synthesis of vitamin D-3 and calcitriol dimers as potential chemical inducers of vitamin D receptor dimerization, J ORG CHEM, 65(24), 2000, pp. 8290-8296
The design and synthesis of vitamin D-3 dimers 2 and 3 and 1 alpha ,25-dihy
droxyvitamin D-3 (calcitriol) dimers 4 and 5 are described. The dimers were
designed with a view to doubly binding the vitamin D receptor (VDR) and in
ducing the receptor homodimerization. In the dimers the units are linked th
rough the C-ll position in ring C by an alkyl side chain of six or 10 carbo
n atoms, far from the hydroxy groups responsible for the VDR binding. The l
inker is formed by olefin metathesis of an olefinic side chain at the C-11
position introduced by stereoselective cuprate addition. The synthesis, whi
ch is both short and convergent, uses the Wittig-Horner approach to constru
ct the vitamin D triene system and allows the preparation of dimers with a
Linker of modulated length with the purpose of optimizing the vitamin D-3-V
DR interaction.