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）：该项目的两个目标是炔烃和醛的催化耦合反应的发展（第1节）以及炔烃和艾因斯（第2节）。这些方法分别在同一操作中影响碳碳键的形成和降低或烷基化，分别提供烯丙基醇和烯丙基胺。这些反应的产物在制备具有治疗益处的更复杂的分子时是有用的“手性构建块”。在第3节中，将炔烃和醛的不对称催化还原耦合用作大环化或碎片偶联的方法，用于terpestacin和fusa​​proliferin的总合成。 Terpestacin抑制HIV感染的进展，IT（或与结构相关的分子）可以提供一种可以治疗AIDS的新手段。 David Chan教授（Caltech Biology）已经开发了必要的测定法，并表示对研究Terpestacin的作用机理非常兴趣。在与L节相关的初步研究中，已经为某些类型的炔烃开发了高度对映选择性的催化催化还原耦合（高达95％的EE），并导致了可能更具选择性和/或更一般的新型配体设计。对于其他类型的炔烃，根据初步结果，另一种新型的手性磷酸配体似乎是优越的。与第2节相关的初步研究表明，某些IMINE是分子内和分子间的三个成分偶联反应中的有效耦合伴侣，其中来自有机烷试剂的组也纳入了四碱成立的烯丙基氨基胺产物中。与第3节有关的初步研究集中在制备晚期合成中间体，并证明了催化片段偶联反应的可行性。