Convergent Synthesis via Asymmetric Catalysis

通过不对称催化的收敛合成

• 批准号: 6856531
• 负责人: Timothy F Jamison
• 金额: $ 31.87万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6856531
• 关键词: aldehydes; alkynes; antiAIDS agent; boranes; catalyst; chemical synthesis; cyclization; imines; organometallic compounds; phosphines; stereochemistry

DESCRIPTION (provided by applicant): Two of the goals of this project are the development of catalytic coupling reactions of alkynes and aldehydes (Section 1) and of alkynes and imines (Section 2). These methods effect a carbon-carbon bond formation and either a reduction or alkylation in the same operation, providing allylic alcohols and allylic amines, respectively. The products of these reactions are useful "chiral building blocks" in the preparation of more complex molecules with therapeutic benefits. In Section 3, asymmetric catalytic reductive coupling of alkynes and aldehydes is used as a means of macrocyclization or fragment coupling in the total synthesis of terpestacin and fusaproliferin. Terpestacin inhibits the progression of HIV infection, and it (or structurally related molecules) may provide a new means with which AIDS can be treated. Prof. David Chan (Caltech Biology) has developed the necessary assays for and has expressed a strong interest in studying terpestacin's mechanism of action. In preliminary studies related to Section l, highly enantioselective catalytic reductive couplings of alkynes and aldehydes (up to 95 percent ee) have been developed for certain types of alkynes and have led to the design of novel ligands that may be more selective and/or more general. For other types of alkynes another novel chiral phosphine ligand appears to be superior based on preliminary results. Initial studies related to Section 2 have shown that certain imines are effective coupling partners in both intramolecular and intermolecular three component coupling reactions, in which a group from an organoborane reagent is also incorporated in the tetrasubstituted allylic amine product. Preliminary studies related to Section 3 have focused on the preparation of advanced synthetic intermediates and have demonstrated the feasibility of the catalytic fragment coupling reactions.

描述（由申请人提供）：本项目的两个目标是开发炔和醛（第1节）以及炔和亚胺（第2节）的催化偶联反应。这些方法在同一操作中实现碳-碳键形成和还原或烷基化，分别提供烯丙醇和烯丙胺。这些反应的产物在制备具有治疗益处的更复杂的分子中是有用的“手性构件”。在第三部分中，炔和醛的不对称催化还原偶联被用作大环化或片段偶联的手段，用于全合成terpestacin和fusaproliferin。Terpestacin抑制HIV感染的进展，它（或结构上相关的分子）可能提供一种治疗艾滋病的新方法。大卫陈教授（加州理工学院生物学）已经开发了必要的检测方法，并表示对研究terpestacin的作用机制有浓厚的兴趣。在与第1部分相关的初步研究中，已经针对某些类型的炔开发了炔和醛的高对映选择性催化还原偶联（高达95%ee），并且已经导致了可能更具选择性和/或更通用的新型配体的设计。对于其他类型的炔，另一种新的手性膦配体似乎是上级的基础上的初步结果。与第2节相关的初步研究表明，某些亚胺在分子内和分子间三组分偶联反应中都是有效的偶联配偶体，其中来自有机硼烷试剂的基团也掺入四取代烯丙基胺产物中。与第3节相关的初步研究集中在高级合成中间体的制备上，并证明了催化片段偶联反应的可行性。