CONJUGATE ADDITIONS WITH A BIMETALLIC CATALYST

将添加剂与双金属催化剂共轭

• 批准号: 6518890
• 负责人: JEREMY T. STARR
• 金额: $ 3.83万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6518890
• 关键词: biological products; carbonyl compound; catalyst; chemical conjugate; chemical synthesis; esters; ketones; metal complex; postdoctoral investigator; stereochemistry

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.

一类新的手性手性催化剂用于酮或酯与a，b-不饱和酰亚胺的直接共轭加成反应。加成产物具有用于合成药物和生物活性天然产物中发现的重要结构基序的有用功能。用一系列金属对和配体取代筛选催化剂以优化反应性。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至少一种起始材料在加成之前转化为反应性前体。任何不需要特殊前体而实现相同转化的方法本质上都更有效（并且对于药物的制造来说更具有成本效益）。直接共轭加成法，然后应用于全合成的台湾五味子素C，一种天然产物，具有活性，对肝癌，结肠癌，癌症和宫颈癌。