Synthesis and vitamin D receptor affinity of 16-oxa vitamin D3 analogues
Kouta Ibe1, Takeshi Yamada1, Sentaro Okamoto1
1Department of Materials and Life Chemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan. okamos10@kanagawa-u.ac.jp.
Abstract:
Two novel 16-oxa-vitamin D3 analogues were synthesized using a tandem Ti(ii)-mediated enyne cyclization/Cu-catalyzed allylation, Ru-catalyzed ring-closing metathesis reaction, and a low-valent titanium (LVT)-mediated stereoselective radical reduction of 8α,14α-epoxide as the key steps for the synthesis of the 16-oxa-C,D ring unit. The vitamin D receptor-binding affinity of the synthesized analogues, 16-oxa-1α,25-(OH)2VD3 and 16-oxa-19-nor-1α,25-(OH)2VD3, was evaluated by fluorescence polarization vitamin D receptor competitor assay and time-resolved fluorescence energy transfer vitamin D receptor co-activator assay.
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