Stereoselective synthesis of annular 9-cis-retinoids and binding characterization to the retinoid X receptor.
Stereoselective synthesis of annular 9-cis-retinoids and binding characterization to the retinoid X receptor.
复制标题
环状 9-顺式-类视黄醇的立体选择性合成及其与类视黄醇 X 受体的结合表征。
DOI：
10.1021/jo0257391
复制
发表时间：
2002
影响因子：
3.6
通讯作者：
Á. D. De Lera
中科院分区：
文献类型：
--
作者：
M. Otero;A. Torrado;Y. Pazos;F. Sussman;Á. D. De Lera
在 C19 和 C10 位置之间掺入脂环族环的 9-顺式视黄酸类似物已被合成并评估为 RXRα 核受体的配体。这些构型受限的类维生素A的立体控制合成结合了Stille交叉偶联和Wittig反应作为关键的成键步骤。 β-溴-α,β-不饱和醛 5 到二烯基锡烷 6 的钯催化交叉偶联反应在室温下非常快，并且在保持二烯基锡烷几何结构的情况下发生。高度立体选择性的 Wittig 反应提供了将疏水环连接到类视黄醇侧链的 C7-C8 键。确定了这些化合物对受体的结合亲和力，并使用分子力学方案表征了环状 9-顺式视黄酸衍生物对 RXRα 核受体的亲和力背后的结构和能量原理。
Analogues of 9-cis-retinoic acid incorporating an alicyclic ring between the C19 and C10 positions have been synthesized and evaluated as ligands for the RXRalpha nuclear receptor. The stereocontrolled synthesis of these configurationally constrained retinoids combines a Stille cross-coupling and the Wittig reaction as key bond-forming steps. The palladium-catalyzed cross-coupling reaction of the beta-bromo-alpha,beta-unsaturated aldehydes 5 to dienylstannane 6 is very fast at room temperature, and takes place with preservation of the dienylstannane geometry. A highly stereoselective Wittig reaction afforded the C7-C8 bond connecting the hydrophobic ring to the retinoid side chain. The binding affinities of these compounds for the receptor were determined, and the structural and energetic rationale behind the affinity profile of the cyclic 9-cis-retinoic acid derivatives for the RXRalpha nuclear receptor was characterized by using Molecular Mechanics protocols.