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.

报道了一种简明高效的玫瑰亲油素全合成方法。 建议。亲玫瑰素是一种独特且非常不寻常的ANSA桥联 从培养物中分离出的氮杂呋喃天然产物 灰绿色链霉菌的肉汤。天然产品展示 亚微磨牙对几种人肿瘤细胞株的杀伤活性 浓缩性，因此是一种有吸引力的铅化合物 药物开发，尤其是因为这种化合物可能 代表了一种不同寻常的行动机制。 正在提出的化学合成利用了一种方法 形成了非常适合于此的中心环结构 目标。这一不明显的策略的应用使我们有可能 用十个线性步骤组装整个核心结构。就这样， 全合成成为制备天然产物的有效手段 材料，也用于制备天然的功能类似物 产品。关键环化反应的对映选择性版本 将在一般上下文中开发，然后应用于 玫瑰亲油素合成。因为分子的绝对立体化学 天然产物还没有确定，这个问题将得到回答 通过全合成。 嵌入在玫瑰亲油素三环中的关键结构 核心，交叉共轭的环戊酮，也存在于许多 其他具有药理活性的天然产物，因此 拟议的研究范围很广。这样做的长期目标之一是 工作是应用对映体选择性环化的关键版本 对这些结构的合成的反应。