CONJUGATE ADDITIONS WITH A BIMETALLIC CATALYST

一类新型手性双金属催化剂被应用于酮或酯与a，b-不饱和亚胺的直接共轭加成反应。加成产物具有合成药物和生物活性天然产物中重要结构基序的有用功能。催化剂通过一系列金属对和配体取代进行筛选，以优化反应活性。直接加成方法很有吸引力，因为许多现有的不对称加成反应需要至少一种起始原料在加成前转化为活性前体。任何不需要特殊前体就能完成同样转化的方法本身就会更有效率(对于制药生产来说也更具成本效益)。然后将直接共轭加成方法应用于taiwanschirin C的全合成，taiwanschirin C是一种具有抗肝癌、结肠癌、癌症和宫颈癌活性的天然产物。

A new family of chiral bimetallic catalysts is applied to the direct conjugate addition of ketones or esters to a,b-unsaturated imides. The addition products possess useful functionality for the synthesis of important structural motifs found in drugs and biologically active natural products. The catalysts are screened with a series of mental pairs and ligand substitutions to optimize reactivity. Direct addition methods are attractive because many existing enantioselective addition reactions require at least one starting material to be converted to a reactive precursor prior to addition. Any method which accomplishes the same transformation without the need for a special precursor would be inherently more efficient (and more cost effective for the manufacture of pharmaceuticals). Direct conjugate addition methodology is then applied to the total synthesis of taiwanschirin C, a natural product with activity against hepatoma, colon, cancer, and cervical cancer.