串联反应能有效提高复杂多环生物碱全合成的效率，自由基串联反应可为此提供更多的选择和手段。细胞松弛素生物碱Phomasin C具有多取代氢化异吲哚酮并和11元大环的三环复杂结构，对结肠腺癌细胞HT29具有很强的抑制活性，IC50值达到7.4 g/mL，至今尚未有全合成报道。本项目计划以Phomasin C的不对称全合成为目标，发展以仲酰胺为底物与醛（酮）和活泼烯烃在一氯二茂钛催化下的新型三组分自由基串联反应；进而,探索手性一氯二茂钛催化下的新型三组分不对称自由基串联反应；并在此基础上通过研究多取代氢化异吲哚酮的不对称合成，结合新的大环构建策略，最终实现这一复杂三环生物碱的高效不对称全合成。该项目的研究可为结构类似的系列细胞松弛素生物碱的不对称全合成提供全新的方法与策略。

Cascade reactions provide an efficient means to construct complex polycyclic alkaloids in a single process. Cascade radical reactions are unique and complementary to those classical ones, such as tandem iminium cascade, which provide novel ideas and means in organic synthesis. In this project, a novel titanocene-catalyzed cascade radical reaction of three components, secondary aminds with aldehydes/ ketones and activated alkenes, will be developed for constructions of a C-N bond and a C-C bond in an one-pot procedure. Furthermore, an asymmetric protocol of this cascade radical reaction also will be studied by using the chiral titanocene catalysts, which will be applied for the asymmetric synthesis of the highly substituted hydroisoindolones. Beginning with this methodology, an efficient synthetic route, involving a novel strategy for construction of the 11-member macrocyclic ring, will be established for asymmetric total synthesis of the cytochalasan alkaloid phomasin C, which exhibits a potent inhibitory activity against HT29 colonic adenocarcinoma cells with IC50 value of 7.4 g/mL.