Department of Chemistry of Medicinal Natural Products, Sichuan University, No. 17, Duan 3, Renmin Nan Road, Chengdu 610041, PR China.
Org Biomol Chem. 2012 Jan 14;10(2):361-6. doi: 10.1039/c1ob06535a. Epub 2011 Nov 14.
The synthesis of a novel D-ring modified docetaxel analogue, in which the oxetane ring is replaced with a γ-lactone, was achieved from 10-deacetylbaccatin III. The key steps of the synthesis include the direct acetylation of the secondary hydroxyl group at C-5 and D-ring opening and intramolecular aldol reaction to form the γ-lactone. In MTT assays, this analogue proved to have equipotent cytotoxicity relative to paclitaxel towards HCT8, HePG2 and BGC23 cancer cell lines, and be more potent than paclitaxel against A549 and A375. It represents the first example of D-ring modified taxoids with significant cytotoxicity.
从 10-去乙酰基紫杉醇 III 中合成了一种新型的 D 环修饰的多西他赛类似物，其中将氧杂环丁烷环替换为γ-内酯。合成的关键步骤包括 C-5 位仲羟基的直接乙酰化和 D 环的开环以及分子内羟醛缩合反应形成γ-内酯。在 MTT 测定中，与紫杉醇相比，该类似物对 HCT8、HePG2 和 BGC23 癌细胞系显示出相当的细胞毒性，并且对 A549 和 A375 的活性比紫杉醇更强。它代表了具有显著细胞毒性的 D 环修饰的紫杉烷类的第一个例子。
