Totalsynthese des mikrobiellen Naturstoffs Collinolacton aus Streptomyces sp. und Darstellung ausgewählter Derivate für biologische Untersuchungen

链霉菌微生物天然产物可里内酯的全合成。

• 批准号: 57259830
• 负责人: Professor Dr. Paultheo von Zezschwitz
• 金额: --
• 依托单位: Fachbereich 15: Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/57259830?language=en
• 关键词: Totalsynthese; des; mikrobiellen; Naturstoffs; Collinolacton

The new secondary metabolite collinolactone was isolated from Streptomyces sp. by Grond et al. and features a rather unusual tricyclic core structure, consisting of a central ten-membered ring with anellated six- and seven-membered lactone moieties. Derivates of the natural product show a remarkable cytostatic activity and lead to formation of monoastral spindles in mitosis. The aim of this project is the first stereoselective total synthesis with formation of the ten-membered ring as central scientific challenge. Similar structures have so far not been prepared, thus, new synthetic routes have to be tested, e.g. an olefin metathesis for closure of the strained ten-membered ring.Altogether, an efficient, 19-step synthesis shall be elaborated which also allows for preparation of isotope-labeled biosynthetic precursors for feeding experiments as well as structure analogs of collinolactone. Thus, the first total synthesis of this natural product will also lead to elucidation of its biosynthesis, its structure-activity-relationships and its binding site. Together with collaboration partners, a complete understanding of collinolactone and its biologic potential shall thus be gained.

新的次级代谢产物collinolactone是由Grod等人从链霉菌属中分离出来的，具有相当不寻常的三环核心结构，由一个中心十元环和六元和七元内酯部分组成。天然产物的衍生物显示出显著的细胞抑制活性，并导致有丝分裂中的单星纺锤体的形成。该项目的目标是首次立体选择性全合成，其中十元环的形成是核心科学挑战。类似的结构迄今尚未制备，因此，必须测试新的合成路线，例如用于封闭应变的十元环的烯烃复分解。总之，应详细说明一种有效的19步合成，其还允许制备用于喂养实验的同位素标记的生物合成前体以及科林内酯的结构类似物。因此，这种天然产物的首次全合成也将导致其生物合成，其结构-活性关系及其结合位点的阐明。与合作伙伴一起，将获得对科林内酯及其生物学潜力的全面了解。