CYCLOPENTANNELATION IN TOTAL SYNTHESIS

全合成中的环戊烯连接

• 批准号: 6180963
• 负责人: Marcus Antonius Tius
• 金额: $ 11.05万
• 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/6180963
• 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.

一种简洁、高效的玫瑰亲和素全合成方法 建议的。 Roseophilin 是一种独特且非常不寻常的 ansa 桥 从培养物中分离出来的氮杂富烯天然产物 灰绿链霉菌肉汤。 天然产品显示 对亚微摩尔数种人类肿瘤细胞系的活性 浓度，因此是一种有吸引力的先导化合物 药物开发，更是如此，因为这种化合物可能 代表了一种不寻常的作用机制。 正在提议的化学合成利用了一种方法 创建非常适合此目的的中心环结构 目标。 应用这种非显而易见的策略可以 通过十个线性步骤组装整个核心结构。 这样， 全合成成为制备天然产物的有效手段 材料，也可用于制备天然物质的功能类似物 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 亲玫瑰素的合成。 由于绝对立体化学 天然产物尚未确定，该问题将得到解答 通过全合成。 嵌入亲玫瑰素三环内的关键结构 交叉共轭环戊烯酮的核心也存在于许多 其他具有药理活性的天然产物，因此 拟议的研究范围广泛。 本次活动的长期目标之一 工作是应用关键环化的对映选择性版本 这些结构的合成反应。