Development of New Catalytic and Enantioselective Reactions

新催化和对映选择性反应的发展

• 批准号: 7227539
• 负责人: AMIR H HOVEYDA
• 金额: $ 30.83万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7227539
• 关键词: 3-hydroxybutanal; Acids; Address; Air; Alcohols; Alkylation; Amines; Amino Acids; Carbon; Chemistry; Class; Development; Eligibility Determination; Exclusion; Goals; Ketones; Ligands; Medicine; Methods; Molecular Weight; Optics; Organic Synthesis; Preparation; Procedures; Protocols documentation; Range; Reaction; Reagent; Screening procedure; Sleep Initiation and Maintenance Disorders; Solvents; Therapeutic Agents; Time; Variant; base; catalyst; cyclic amine; high throughput screening; nitroalkane; programs; tertiary amine

DESCRIPTION (provided by applicant): High yielding and selective preparation of chiral organic molecules is critical to the availability of therapeutic agents. Development of catalytic, enantioselective synthetic methods is a compelling objective in chemistry and medicine. Among the most useful building blocks in organic synthesis are optically pure amines and alcohols; our program will address issues regarding enantioselective preparation of these important classes of molecules. We will establish new, practical, and efficient and highly enantioselective methods for the synthesis of secondary and tertiary amines and alcohols that are otherwise difficult to obtain in high yield and optical purity. One main goal of our program is the development of new chiral ligands and catalysts, all of which are amino acid-based. A crucial advantage of amino acid-based molecules is that they can be easily prepared and modified, allowing for rapid (mechanism-driven) synthesis and screening of variants so that catalysts that best fit a specific set of transformations can be identified expeditiously. We will develop new amino acid-based chiral ligands and practical methods for efficient enantioselective additions of enolsilanes and nitroalkanes to aldimines (Mannich reactions). Catalyst discovery will be guided by mechanistic principles and will be accomplished by screening protocols developed in this program. The new synthetic methods will offer practical (distilled solvents, air exclusion not required) and unique procedures for the synthesis of various acyclic and cyclic amines that cannot be prepared by alternative catalytic enantioselective methods. We will also develop new amino acid-based chiral ligands and methods for efficient enantioselective additions of carbon nucleophiles to ketoimines. The aforementioned principles will be used in the development of catalytic asymmetric alkylations and Mannich reactions that provide access to optically enriched alpha- and beta-quaternary amino acids. We will also develop new chiral amino acid-based ligands, catalysts and methods for efficient enantioselective synthesis of alcohols. Amino acid-based chiral ligands will be developed that effect Ag-catalyzed asymmetric aldol additions for a range of enolsilanes to various ketones. Finally, a new class of low molecular weight and easily available amino acid-based chiral catalysts will be developed for enantioselective silylations of alcohols. In all studies utility in the preparation of biologically active compounds in high optical purity will be demonstrated.

描述（由申请人提供）：手性有机分子的高产率和选择性制备对于治疗剂的可用性至关重要。发展催化的、对映选择性的合成方法是化学和医学中一个引人注目的目标。在有机合成中最有用的积木是光学纯胺和醇;我们的计划将解决这些重要类别的分子的对映选择性制备的问题。我们将建立新的，实用的，有效的和高度对映选择性的方法，用于合成仲胺和叔胺和醇，否则很难获得高产率和光学纯度。我们计划的一个主要目标是开发新的手性配体和催化剂，所有这些都是基于氨基酸的。基于氨基酸的分子的一个关键优势是它们可以很容易地制备和修饰，允许快速（机制驱动）合成和筛选变体，从而可以快速鉴定最适合特定转化的催化剂。我们将开发新的氨基酸为基础的手性配体和有效的烯醇硅烷和硝基烷醛亚胺（曼尼希反应）的对映选择性加成的实用方法。催化剂的发现将由机械原理指导，并将通过本计划中开发的筛选协议来完成。新的合成方法将提供实用的（蒸馏溶剂，不需要排除空气）和独特的程序，合成各种非环状和环状胺，不能通过替代催化对映选择性方法制备。我们也将开发新的氨基酸为基础的手性配体和方法，有效的对映选择性加成碳亲核试剂酮亚胺。上述原理将用于催化不对称烷基化和曼尼希反应的开发，这些反应提供了获得光学富集的α-和β-季氨基酸的途径。我们还将开发新的手性氨基酸为基础的配体，催化剂和方法，有效的不对称合成醇。将开发基于氨基酸的手性配体，其影响Ag催化的不对称羟醛加成，用于一系列烯醇硅烷与各种酮的加成。最后，一类新的低分子量和容易获得的氨基酸为基础的手性催化剂将被开发用于醇的不对称选择性硅烷化反应。在所有研究中，将证明在制备高光学纯度的生物活性化合物中的实用性。