Mukaiyama Aldol Strategy Towards the Leptosin Alkaloids

向山羟醛策略针对瘦素生物碱

• 批准号: 6890315
• 负责人: AARON D WROBLESKI
• 金额: $ 4.19万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-05 至 2006-03-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6890315
• 关键词: alcohols; aldehydes; alkaloids; biological products; chemical reaction; chemical structure function; chemical synthesis; method development; piperazines; postdoctoral investigator; pyrrolidines; stereochemistry

DESCRIPTION (provided by applicant): The leptosins are a class of natural products presenting remarkable molecular complexity and potent cytotoxic and antitumor activity. Thus far, no reports documenting the total synthesis of any of these alkaloids has been published. One of the more complex challenges such a synthesis must address is the stereocontrolled formation of the central bispyrrolidinoindoline ring system containing consecutive all-carbon quaternary centers and two secondary alcohols. It is proposed that using a one-pot double Mukaiyama aldol reaction will allow for the installation of both quaternary centers and adjacent secondary alcohols. Before this reaction can be used to install the above stereogenic centers, it is necessary to understand the stereocontrolling elements of the reaction. With that, before undertaking any total syntheses preliminary studies will focus on examining how varying the structures of the reactive components of the Mukaiyama aldol dictate reaction stereocontrol. Once the stereocontrolling elements of this reaction are understood, a proposal towards completing the total syntheses of leptosins C and K will be presented.

描述（由申请人提供）： 瘦素是一类天然产物，具有显着的分子复杂性和有效的细胞毒性和抗肿瘤活性。迄今为止，尚未发表任何记录这些生物碱的全合成的报告。这种合成必须解决的更复杂的挑战之一是包含连续全碳季中心和两个仲醇的中心双吡咯烷二氢吲哚环系统的立体控制形成。建议使用一锅双 Mukaiyama 羟醛反应来安装季中心和相邻的仲醇。在使用该反应安装上述立体中心之前，有必要了解该反应的立体控制元件。因此，在进行任何全合成之前，初步研究将集中于研究 Mukaiyama 羟醛反应组分的结构变化如何决定反应立体控制。一旦了解了该反应的立体控制元件，就会提出完成瘦素 C 和 K 的全合成的建议。