SYNTHESIS OF THAPSIGARGIN ANALOGS

毒胡萝卜素类似物的合成

• 批准号: 2011104
• 负责人: JAMES H MEYER
• 金额: $ 2.43万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-26 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2011104
• 关键词: analog; chemical synthesis; method development; thapsigargin; tumor promoters

The proposed research explores a synthetic strategy which will provide access to analogs of the tumor promoter thapsigargin (1). New adaptations of two metal-mediated synthetic methodologies will be examined. First, the synthesis of cycloheptene template 10 will extend available protocols for the selective functionalization of the known chiral allylmolybdenum complex 2. Second, palladium-catalyzed cycloisomerization of enyne 10 will be investigated as a means for forming a highly substituted bicyclo[5.3.0]decane system. Functional group manipulation of the resulting product will be pursued to provide tricyclic compound 21. The specific goals for the postdoctoral appointment are the acquisition of this synthetic target, as well as the validation of the methods mentioned above. However, the enantiomerically enriched target 21 represents a potentially general precursor for the preparation of analogs of thapsigargin and other guaiane natural products.

拟议的研究探索了一种综合战略， 获得肿瘤促进剂毒胡萝卜素的类似物（1）。新 两种金属介导的合成方法的适应将是 考察首先，环庚烯模板10的合成将扩展到 用于选择性官能化已知化合物的可用方案 手性烯丙基钼配合物2.第二，钯催化 将研究烯炔10的环异构化作为 形成高度取代的双环[5.3.0]癸烷体系。功能 将对最终产品进行分组操作，以提供 三环化合物21.博士后的具体目标 任命是收购这一合成目标，以及 验证上述方法。但 对映体富集的靶21代表了潜在的一般性 用于制备毒胡萝卜素和其它类似物的前体 愈创木烷天然产品。