Synthesis and vitamin D receptor affinity of 16-oxa vitamin D3 analogues
Synthesis and vitamin D receptor affinity of 16-oxa vitamin D3 analogues
复制标题
DOI：
10.1039/c9ob02339a
复制
发表时间：
2019-12-28
影响因子：
3.2
通讯作者：
Okamoto, Sentaro
中科院分区：
文献类型：
--
作者：
Ibe, Kouta;Yamada, Takeshi;Okamoto, Sentaro
采用串联的Ti（ii）介导的烯炔环化/Cu催化的烯丙基化、Ru催化的闭环复分解反应和低价钛（LVT）介导的立体选择性自由基还原8 α，14 α-环氧化合物作为合成16-oxa-C，D环单元的关键步骤，合成了两种新的16-oxa-vitamin D-3类似物。合成的类似物16-oxa-1 alpha，25-（OH）（2）VD 3和16-oxa-19-nor-1 alpha，25-（OH）（2）VD 3的维生素D受体结合亲和力通过荧光偏振维生素D受体竞争剂测定和时间分辨荧光能量转移维生素D受体共激活剂测定进行评价。
Two novel 16-oxa-vitamin D-3 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 8 alpha,14 alpha-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-1 alpha,25-(OH)(2)VD3 and 16-oxa-19-nor-1 alpha,25-(OH)(2)VD3, was evaluated by fluorescence polarization vitamin D receptor competitor assay and time-resolved fluorescence energy transfer vitamin D receptor co-activator assay.