CYCLOPENTANNELATION IN TOTAL SYNTHESIS

全合成中的环戊烯连接

• 批准号: 2670514
• 负责人: Marcus Antonius Tius
• 金额: $ 10.57万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2670514
• 关键词: antineoplastic antibiotics; biological products; cyclization; cyclopentane; drug design /synthesis /production

A concise and efficient total synthesis of roseophilin has been proposed. Roseophilin is a unique and very unusual ansa-bridged azafulvene natural product which has been isolated from the culture broths of Streptomyces griseoviridis. The natural product shows activity against several human tumor cell lines in submicromolar concentration and is therefore an attractive lead compound for pharmaceutical development, the more so since this compound may represent an unusual mechanism of action. The chemical synthesis which is being proposed makes use of a method for creating the central ring structure which is ideally suited to this target. Application of this non-obvious strategy makes it possible to assemble the entire core structure in ten linear steps. In this way, total synthesis become an efficient means for preparing both the natural material and also for preparing functional analogs of the natural product. The enantioselective version of the key cyclization reaction will be developed in a general context and then applied to the roseophilin synthesis. Since the absolute stereochemistry of the natural product has not been determined, the question will be answered through total synthesis. The key structure which is embedded within the roseophilin tricyclic core, the cross-conjugated cyclopentenone, is also present in a number of other pharmacologically active natural products, therefore the proposed research is broad in scope. One of the long-term goals of this work is to apply the enantioselective version of the key cyclization reaction to the syntheses of these structures.

本文报道了一种简便、有效的亲玫瑰素的全合成方法。 提出了 Roseophilin是一种独特的和非常不寻常的柄桥 从培养物中分离的氮杂富烯天然产物 灰绿链霉菌的肉汤。 天然产物显示 亚微摩尔浓度下对几种人肿瘤细胞系的活性 浓度，因此是一种有吸引力的铅化合物， 药物开发，因为这种化合物可能 代表了一种不寻常的作用机制 正在提出的化学合成利用了一种方法， 形成理想地适合于此的中心环结构 目标 应用这种非显而易见的策略， 在十个线性步骤中组装整个核心结构。 通过这种方式， 全合成成为一种有效的手段， 材料，并且还用于制备天然药物的功能类似物。 产品 关键环化反应的对映选择性版本 将在一般背景下开发，然后应用于 亲玫瑰素合成 由于绝对立体化学的 天然产物尚未确定，问题将得到回答 通过全合成。 嵌入亲玫瑰素三环内的关键结构 核心，交叉共轭环戊烯酮，也存在于一些 其他活性天然产物，因此， 拟议的研究范围广泛。 这个项目的长期目标之一 工作是应用键环化的对映选择性版本 这些结构的合成反应。