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中文摘要
翻译
拟议的研究将集中在围绕开发和应用的广泛目标上 的镍催化,硅烷促进的醛和炔的还原偶联,以生成烯丙基 酒精。烯丙醇是许多生物学和医学上重要的化合物中常见的结构基序。 化合物以及用于广泛的有机反应和催化过程的通用前体。 基础研究将集中在理解这种新的耦合过程的机制和范围, 以及开发新的区域选择性、非对映选择性和对映选择性变体。的另一主要目的 拟议的项目期间是开发一种新的程序,用于直接组装糖基化的 大环从一个简单的无环炔醛,这将大大简化碳水化合物的制备, 官能化大环化合物。 在天然和非天然大环内酯类化合物合成中的应用将是研究计划的一个重要重点。 天然存在的大环内酯构成了一个大家族的生物活性大环天然产物, 这一组中的许多成员具有碳水化合物附加物, 识别事件是其生物活性的关键。该类成员的抗生素活性是 广泛记录和临床重要性,以及许多其他生物活性模式, 记录了这类化合物。特异性靶向的结构包括阿加霉素D, amphidinomycin W和7-O-(α-葡糖基)-2,3-二氢cineromycin B,以及新的镍催化反应 将作为每一个合成的关键步骤。除了制定一些方法外, 大环内酯天然产物,我们提出的糖基化大环组装方法将用于 访问新的结构,将由大卫谢尔曼的研究小组作为基板, 细胞色素P450催化氧化。这项合作研究将阐明基板范围, 细胞色素P450氧化,并可能导致新的化合物作为治疗剂的潜力。
英文摘要
The proposed research will focus on a broad set of aims that center around the development and application of the nickel-catalyzed, silane-promoted reductive coupling of aldehydes and alkynes to generate allylic alcohols. Allylic alcohols are a common structural motif in many biologically and medicinally important compounds as well as versatile precursors for a broad array of organic reactions and catalytic processes. Fundamental studies will focus on understanding the mechanism and scope of this novel coupling process, and on developing new regioselective, diastereoselective, and enantioselective variants. An important aim of the proposed project period is the development of a new procedure for the direct assembly of a glycosylated macrocycle from a simple acyclic ynal, which will significantly simplify the preparation of carbohydrate- functionalized macrocycles. Applications in synthesis of natural and unnatural macrolides will be an important focus of the research plan. Naturally occurring macrolides make up a large family of biologically active macrocyclic natural products, and many members of this group possess carbohydrate appendages that greatly impact the molecular recognition events that are key in their biological activity. The antibiotic activities of members of this class are widely documented and clinically important, and many other modes of biological activity have been documented for this class of compounds. The structures specifically targeted include aigialomycin D, amphidinolide W, and 7-O-(alpha-glucosyl)-2,3-dihydrocineromycin B, and novel nickel-catalyzed reactions will be used as key steps in each of the syntheses. In addition to developing approaches to several macrolide natural products, our proposed method for assembly of glycosylated macrocycles will be used to access novel structures that will examined by the research group of David Sherman as substrates for cytochrome P450-catalyzed oxidations. This collaborative research will elucidate the substrate scope in cytochrome P450 oxidations and may lead to new compounds with potential as therapeutic agents.
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Michigan Chemistry-Biology Interface Training Program
Catalytic Methods for Building Block Assembly and for Stereoselective Glycosylation
Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis
Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis
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