Intramolecular Metal-Catalyzed Alkene (2+2}Cycloaddition

分子内金属催化烯烃 (2 2}环加成

• 批准号: 6455193
• 负责人: MICHAEL J KRISCHE
• 金额: $ 18.75万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 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 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6455193
• 关键词: alkenes; antimitotics; bicyclic compound; biological products; catalyst; chemical addition; cyclization; metals; stereochemistry

DESCRIPTION: (provided by applicant) Despite a wealth of research pertaining to metal catalyzed cycloadditions, to date, there are no reports of metal catalysts for intramolecular alkene (2+2)cycloaddition. We herewith describe the first metal catalyst for intramolecular cyclobutanation. This methodology allows for facile assembly of bicyclo(3.2.0)heptane ring systems. Related photochemical processes generally exhibit poor levels of stereoselectivity and are inefficient for acyclic substrates due to quenching of the excited state via alkene isomerization. In contrast, our metal catalyst for alkene (2+2)cycloaddition is viable for acyclic precursors and all cycloadducts are obtained as single stereoisomers. This methodology will be utilized in a general synthetic approach to members of the bourbonane and spatane families of natural products. Certain members of the spatane family strongly inhibit cell division in human melanoma and 224C astrocytoma neoplastic cell lines. Spatol's antimitotic activity is attributed to inhibition of microtubule assembly. Finally, strategies for development of enantioselective variants of this methodology are outlined.

描述：（由申请人提供）尽管有大量关于金属催化环加成的研究，但迄今为止，还没有金属催化环加成反应的报道。 分子内烯烃(2+2)环加成催化剂。我们在此描述 第一个用于分子内环丁烷化的金属催化剂。这种方法论 允许轻松组装双环(3.2.0)庚烷环系统。相关的光化学过程通常表现出较差的立体选择性和 由于激发态的猝灭，对于无环底物效率低下 通过烯烃异构化。相比之下，我们的烯烃金属催化剂 (2+2)环加成对于无环前体是可行的，并且所有环加合物都是 以单一立体异构体形式获得。该方法将用于 波旁烷和斯帕烷家族成员的一般合成方法 天然产品。 spatane家族的某些成员强烈抑制细胞 人黑色素瘤和 224C 星形细胞瘤肿瘤细胞系中的分裂。斯帕托的 抗有丝分裂活性归因于微管组装的抑制。 最后，该药物的对映选择性变体的开发策略 概述了方法论。