Total synthesis of (-)-pulvomycin

(-)-普沃霉素的全合成

• 批准号: 236307437
• 负责人: Professor Dr. Thorsten Bach
• 金额: --
• 依托单位: Lehrstuhl für Organische Chemie I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/236307437?language=en
• 关键词: Total; synthesis; pulvomycin

(-)-Pulvomycin is a complex polyketide natural product with a molecular mass of 839 Da, which effectively inhibits the bacterial elongation factor EF-Tu. Structurally, pulvomycin can be divided into a 22-membered macrolactone (eastern fragment) and a linear chain (western fragment), which is connected via a beta-glycosidic bond to labilose, a 6-desoxygalactose. So far, neither a total synthesis of this natural product nor partial syntheses of its individual fragments have been reported. In this project a convergent total synthesis of (-)-pulvomycin is proposed, which is based on the above-mentioned division of the molecular skeleton. The synthetic strategy takes the high lability of the natural product into account, which will be better understood by the synthesis of the individual fragments. The macrolactone of the eastern fragment bears particular importance for the biological activity because plays the major role in binding the biological target molecule. EF-Tu has been previously validated as a target for the development of new antibiotics.

（-）-Pulvomycin是一种复杂的聚酮化合物天然产物，分子量为839 Da，可有效抑制细菌延伸因子EF-Tu。在结构上，普沃霉素可分为22元大环内酯（东部片段）和线性链（西部片段），后者通过β-糖苷键与6-脱氧半乳糖labilose连接。到目前为止，还没有报道这种天然产物的全合成，也没有报道其单个片段的部分合成。本项目在上述分子骨架划分的基础上，提出了（-）-普立霉素的收敛全合成方法。合成策略考虑了天然产物的高不稳定性，这将通过合成单个片段来更好地理解。东部片段的大环内酯对生物活性具有特别重要的意义，因为其在结合生物靶分子中起主要作用。EF-Tu以前已被验证为开发新抗生素的靶标。

项目成果

Studies towards the Synthesis of (–)-Pulvomycin: Construction of the C12–C40 Segment by a Stereoselective Aldol Reaction

(â)-普沃霉素的合成研究：通过立体选择性羟醛反应构建 C12âC40 链段

• DOI: 10.1055/a-1464-2576
• 发表时间: 2021
• 期刊: Synthesis
• 作者: S. Wienhold;L. Fritz;T. Judt;S. Hackl;T. Neubauer;B. Sauerer;T. Bach
• 通讯作者: T. Bach