Department of Chemistry, College of Sciences, Shanghai University, 99 Shangda Road, Baoshan District, Shanghai 200444, China.
Med Chem. 2012 Sep;8(5):789-98. doi: 10.2174/157340612802084379.
Despite numerous synthetic efforts and extensive SAR studies on paclitaxel analogs, little work has been devoted to derive SAR of the C-1 hydroxy group. Up to now, 1-deoxypaclitaxel has only been reported to be isolated from the Chinese yew, Taxus mairei (Taxaceae). However, the isolation from natural sources does not solve the availability problem due to the reported low yield of isolation. Also, only several analogues of this type have been reported. Thus, there is an urgent need for exploration of new synthetic methods on this structurally intriguing molecule and further SAR studies. In present work, we report the initial expedient semi-synthesis of 1-deoxypaclitaxel and its novel analogues with structural variations at C7 and C10 from 1-deoxybaccatin VI, as well as their cytotoxic activities against A 549 cell line.
尽管人们对紫杉醇类似物进行了大量的合成努力和广泛的 SAR 研究，但对 C-1 羟基的 SAR 研究却很少。到目前为止，只有从中国红豆杉（红豆杉科）中分离出 1-去氧紫杉醇。然而，由于报道的分离产率低，从天然来源分离并不能解决可用性问题。此外，这类类似物也只有几种被报道。因此，迫切需要探索这种结构有趣的分子的新合成方法和进一步的 SAR 研究。在本工作中，我们报道了从 1-去氧巴卡丁 VI 出发，通过初步便利的半合成方法制备 1-去氧紫杉醇及其 C7 和 C10 结构变化的新型类似物，并对它们对 A549 细胞系的细胞毒性活性进行了研究。
