Synthesis of Tumor Inhibitory Marine Natural Products

抑癌海洋天然产物的合成

• 批准号: 6633970
• 负责人: JAMES A MARSHALL
• 金额: $ 23.05万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6633970
• 关键词: antineoplastics; butyrolactone; chemical synthesis; diterpenes; drug design /synthesis /production; organometallic compounds; stereochemistry

The total synthesis of a number of marine natural products in the polyketide and diterpene families will be undertaken. The targeted compounds exhibit high levels of growth inhibition against various human tumor cell lines but they are generally not readily available from natural sources in quantities amenable to their evaluation as drug candidates. In addition, we will synthesize analogues of some of the more active compounds that will be tested for differential cytotoxicity against tumor vs. normal human cell lines by Professor F. Valeriote at the Josephine Ford Cancer Center in Detroit. The main chemical issues to be addressed include the control of stereochemistry by means of chiral organometal chemistry and the design of new and efficient routes to structurally novel natural products.

将进行聚酮化合物和二萜家族中一些海洋天然产物的全合成。靶向化合物对各种人肿瘤细胞系表现出高水平的生长抑制，但它们通常不容易从天然来源以适合于作为候选药物进行评价的量获得。此外，我们将合成一些活性更高的化合物的类似物，这些化合物将由F教授测试对肿瘤和正常人类细胞系的不同细胞毒性。瓦莱里奥特在底特律的约瑟芬福特癌症中心。要解决的主要化学问题包括通过手性有机金属化学控制立体化学和设计新的和有效的路线，以结构新颖的天然产物。