Study on structural development of novel 14-epi-19-norprevitamin D type seco-steroids working on bone formation

14-表-2 α-甲基-1 α，25-二羟基-19-去甲维生素D_3是维生素D的一种新骨架。有趣的是，我们发现新化合物通过酸性催化剂差向异构化为14-表-2 α-甲基-1 α，25-二羟基-19-去甲速甾醇，并且速甾醇类似物通过维生素D受体显示出有效的骨钙素启动子反式激活活性。接下来，我们开发了差向异构化合物的直接合成路线，以获得足够量的速甾醇类似物用于体内研究。X射线共结晶学研究解释了速甾醇与维生素D受体的前所未有的结合模式。

As a novel skeleton of vitamin D working on bone formation, 14-epi-2α-methyl-1α, 25-dihydroxy-19-norprevitamin D_3 has been synthesized. Interestingly, we found that the new compound epimerizes to 14-epi-2α-methyl-1α, 25-dihydroxy-19-nortachysterol by acidic catalysts, and the tachysterol analog showed potent osteocalcin promoter transactivation activity through the vitamin D receptor. Next, we developed a direct synthetic route to the epimerized compound to obtain enough amount of the tachysterol analog for in vivo studies. X-ray co-crystallographic studies explained an unprecedented binding mode of the tachysterol to the vitamin D receptor.