CONJUGATE ADDITIONS WITH A BIMETALLIC CATALYST

一种新的手性双金属催化剂应用于甲、乙不饱和亚胺的酮或酯的直接共轭加成。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。通过一系列的心理对和配体取代对催化剂进行筛选，优化催化剂的反应活性。直接加成方法是有吸引力的，因为许多现有的对映选择性加成反应需要在加成之前将至少一种起始物质转化为反应前体。任何在不需要特殊前体的情况下完成相同转化的方法本质上都更有效（并且对药品制造更具成本效益）。然后将直接共轭加成法应用于具有抗肝癌、结肠癌、宫颈癌活性的天然产物台湾灵C的全合成。

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.