Swiss Federal Institute of Technology (ETH) Zürich, Switzerland.
Org Lett. 2010 May 21;12(10):2302-5. doi: 10.1021/ol100665m.
An efficient new synthesis has been elaborated for non-natural (-)-dactylolide ((-)-2) and its 13-desmethylene analogue 4, employing a HWE-based macrocyclization approach with beta-keto-phosphonate/aldehyde 19 and the respective 13-desmethylene derivative as the key intermediates. Both (-)-2 and 4 as well as the corresponding C20 alcohols inhibit human cancer cell proliferation with IC(50) values in the sub-micromolar range and induce the polymerization of tubulin in vitro.
已经详细阐述了一种高效的非天然（-）-达托霉素（（-）-2）及其 13-去甲二烯类似物 4 的新合成方法，该方法采用基于 HWE 的大环化方法，使用β-酮膦酸酯/醛 19 和相应的 13-去甲二烯衍生物作为关键中间体。（-）-2 和 4 以及相应的 C20 醇均能以亚微米级浓度抑制人癌细胞增殖，并在体外诱导微管蛋白聚合。
