Total Synthesis of the Diterpenoid Alkaloid Hetisine

二萜生物碱Hetisine的全合成

• 批准号: 7277704
• 负责人: TRAVIS B DUNN
• 金额: $ 3.66万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7277704
• 关键词: 2-benzoquinone; Alkaloids; Carbon; Chemicals; Complex; Diels Alder reaction; Diterpenes; Family; Masks; Object Attachment; Reaction; Relative (related person); Research; Skeleton; member; nonane; o-Benzoquinones

DESCRIPTION (provided by applicant): An asymmetric total synthesis of the diterpenoid alkaloid hetisine is proposed. Neither hetisine nor any of its close chemical relatives has been prepared by total synthesis. An asymmetric synthesis of this compound would be an important contribution to the field of alkaloid total synthesis. The pivotal step of the proposed synthesis is an intramolecular Diels-Alder reaction of a masked o-benzoquinone to construct a highly functionalized bicyclo[2.2.2]octene. Other key steps in the synthesis plan include a Mannich-type reaction to build an azabicyclo[3.2.1]nonane core skeleton and a transannular C-H insertion of a diazoketone to establish one of the more challenging carbon-carbon bonds in the hetisine skeleton. The synthesis plan is sufficiently flexible that many of the approximately 100 members of the hetisane family of diterpenoid alkaloids could also be prepared by extension of the synthesis plan presented here.

描述（由申请人提供）：提出了一种二萜生物碱的不对称全合成方法。目前还没有用全合成法制备过hetisine或它的任何化学近亲。该化合物的不对称合成将对生物碱全合成领域做出重要贡献。所提出的合成的关键步骤是掩膜邻苯醌的分子内Diels-Alder反应，以构建高度功能化的双环[2.2.2]辛烯。合成计划中的其他关键步骤包括一个mannich型反应，以构建一个氮杂环[3.2.1]壬烷核心骨架，以及一个重氮酮的跨环碳氢插入，以建立一个更具有挑战性的碳-碳键。合成计划是足够灵活的，许多二萜类生物碱的hetisane家族的大约100个成员也可以通过扩展这里提出的合成计划制备。

项目成果

Asymmetric construction of rings A-D of daphnicyclidin-type alkaloids.

• DOI: 10.1021/ol902373m
• 发表时间: 2009-12-17
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Dunn TB;Ellis JM;Kofink CC;Manning JR;Overman LE
• 通讯作者: Overman LE