Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ont., Canada L8S 4M1.
Bioorg Med Chem Lett. 2010 Apr 1;20(7):2335-9. doi: 10.1016/j.bmcl.2010.01.157. Epub 2010 Feb 4.
seco-Derivatives of the anticancer agent pancratistatin bearing the 2S,3S,4S,5S configuration were accessed via a novel, highly diastereoselective anti-aldol reaction. Structure-activity relationships reveal important insights into the seco-pancratistatin pharmacophore as a potent and selective inhibitor of human cytochrome P450 3A4 (CYP3A4), and highlight features of concern in advancing a potent, selective anticancer agent in the pancratistatin series.
通过一种新颖的、高度非对映选择性的反醛醇反应，获得了具有 2S、3S、4S、5S 构型的抗癌剂 Pancratistatin 的 sec 衍生物。构效关系揭示了 secopancratistatin 药效团作为人细胞色素 P450 3A4（CYP3A4）的有效和选择性抑制剂的重要见解，并强调了在 Pancratistatin 系列中推进有效、选择性抗癌剂时需要关注的特征。
