Asymmetric Reaction Technologies for the Synthesis of Chemotherapeutic Agents

用于合成化疗药物的不对称反应技术

• 批准号: 7430140
• 负责人: SCOTT G. NELSON
• 金额: $ 27.4万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7430140
• 关键词: Acids; Address; Affect; Aldehydes; Alder plant; Apoptosis Regulator; Applications Grants; Biological Factors; Catalysis; Chemicals; Chemistry; Chloride Ion; Chlorides; Cinchona Alkaloids; Compatible; Complex; Development; Facility Construction Funding Category; Family; Foundations; Goals; Health; Human; Imines; In Situ; Ions; Lactams; Lactones; Lead; Libraries; Methodology; Object Attachment; Organic Synthesis; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Play; Preparation; Process; Propionates; Propionic Acids; Propionic acid; Reaction; Relative (related person); Research; Role; Screening procedure; Stereoisomer; Sulfones; Technology; Therapeutic; Variant; alginic acid compound; apoptolidin; base; catalyst; chemotherapeutic agent; cycloaddition; design; diene; dimer; drug development; ketene; method development; monomer; novel; piperidine; small molecule; success; synergism

Small molecule-based drugs continue to provide the foundation for developing therapeutic strategies for treating of most human illnesses. A substantial portion of drug development efforts within medicinal chemistry is, therefore, devoted to the synthesis of compounds for screening as drug candidates. Whether drug development efforts are directed toward specific bioactive targets or the synthesis of a library of selected derivatives, success in these endeavors is critically dependent on concurrent developments in organic synthesis methodology that allows the efficient and economical preparation of the targeted materials. Recognizing the synergism existing between chemistry and industrial drug development, this proposal details the development of new organic reaction methodology designed to access biologically active organic compounds efficiently and economically. Toward this goal, we will develop the reaction technology necessary to realize a general strategy for the catalytic synthesis of polypropionate-derived natural products. The composition of polyketides as repeating acetic or propionic acid units makes a modular synthesis strategy exploiting iterative installation of homologous monomer units an attractive synthesis strategy. Thus, we will develop a modular strategy for the catalytic asymmetric construction of stereochemically diverse polypropionate networks. The relevance of these reaction development activities to medicinal research and human health issues is exemplified in a de novo enantioselective total synthesis of the highly selective apoptosis regulator apoptolidin C. Heterocyclic small molecules are among the most ubiquitous features of new drug hits, important lead compounds, and commercially available pharmaceuticals. The development of a novel family of [4+2] and [2+2] cycloadditions for the asymmetric synthesis of highly substituted piperidine and ¿-lactam derivatives, respectively, is inspired by the central role heterocycles play in pharmaceutical drug development efforts. Furthermore, efforts to develop catalytic asymmetric variants of these cycloadditions are intended to maximize the utility of these reactions in industrial medicinal and process chemical research.

小分子的药物继续为制定治疗策略的基础 治疗大多数人类疾病。医学化学中药物开发工作的很大一部分 因此，IS致力于合成作为候选药物筛查的化合物。是否药物 开发工作针对特定的生物活性目标或合成所选的库 衍生品，在这些努力中的成功取决于有机合成的并发发展 允许有效且经济准备目标材料的方法。认识到 化学与工业药物开发之间存在的协同作用，此提案的详细信息 新的有机反应方法旨在有效访问生物活性有机化合物， 经济上。为了实现这一目标，我们将开发必要的反应技术来实现一般策略 用于催化衍生的天然产物的催化合成。聚酮化合物的组成 重复乙酸或丙酸单元使模块化合成策略利用了迭代安装的安装 同源单体单位是一种有吸引力的综合策略。那就是我们将制定一个模块化策略 立体化学上多样化的聚丙烯网络的催化不对称结构。这些相关性 从头开始说明了对医学研究和人类健康问题的反应发展活动 高度选择性凋亡调节剂凋亡蛋白C的对映选择性总合成。 杂环小分子是新药命中最普遍的特征之一，重要的铅 化合物和市售药品。 [4+2]和 [2+2]用于高度取代的哌啶和� -lactam衍生物的不对称合成的环加成， 分别受杂环在药物开发工作中发挥的核心作用的启发。 此外，开发这些环载的催化不对称变体的努力旨在最大化 这些反应在工业医学和过程化学研究中的效用。