Design and synthesis of novel vitamin D receptor ligands having a functional group that reinforces the interaction with the receptor

合成了一种新型的具有官能团的维生素D受体(VDR)配体，旨在通过一定的氨基酸残基加强与VDR的相互作用。以钯为催化剂，用聚合法合成了维生素D A环上含有羧基而不是重要的1α羟基的配体。此外，还合成了A环C2位螺环氧烷稠合的维生素D类似物。化合物的VDR结合表明，在A环的C2位引入羧基或氧杂环己烷可以在一定程度上补偿1α-羟基的损失，从而生成独特的维生素D类似物。

Novel vitamin D receptor (VDR) ligands having a functional group designed to reinforce the interaction to the VDR through a certain amino acid residue were synthesized. The ligands having a carboxy group in the A-ring of vitamin D instead of the important 1alpha-hydroxy group were synthesized by a convergent method using palladium catalyst. In addition, vitamin D analogues having a spiro-oxetane fused at the C2 position in the A-ring were also synthesized. The VDR binding of the synthesized compounds revealed that the introduction of a carboxy group or an oxetane into the C2 position of the A-ring would compensate the loss of the 1alpha-hydroxy group to a certain extent to generate unique vitamin D analogues.