Institut de Science et Ingénierie Supramoléculaires (ISIS-UMR 7006), Université de Strasbourg CNRS, 8 Allée Gaspard Monge, 67000 Strasbourg, France.
Chemistry. 2012 Jul 16;18(29):8978-86. doi: 10.1002/chem.201200546. Epub 2012 Jun 13.
A concise and modular synthesis of pochonin E and F, and their epimers at C-6 established the correct stereochemistry of these two natural products. Several members of the pochonin family have been shown to bind the heat shock protein 90 (Hsp90), which has been the focus of intense drug discovery efforts. Pochonin E and F as well as their epimers were derivatized into the corresponding pochoximes and further modified at the C-6 position. Molecular dynamics simulations, docking studies, and Hsp90 affinity measurements were performed to evaluate the impact of these modifications.
波考宁 E 和 F 及其 C-6 差向异构体的简洁、模块化合成确定了这两种天然产物的正确立体化学。波考宁家族的几个成员已被证明能与热休克蛋白 90（Hsp90）结合，这一直是药物发现努力的重点。波考宁 E 和 F 及其差向异构体被衍生为相应的波考肟，并在 C-6 位置进一步修饰。进行了分子动力学模拟、对接研究和 Hsp90 亲和力测量，以评估这些修饰的影响。
