Total Synthesis of Curvicollid C

Curvicolid C的全合成

• 批准号: 246978400
• 负责人: Professor Dr. Martin Hiersemann
• 金额: --
• 依托单位: Forschungsgebiet Organische Chemie
• 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 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/246978400?language=en
• 关键词: Total; Synthesis; Curvicollid

The elucidation of the configuration of natural products and the supply of derivatives for biological studies is of premiere importance. In this regard, the aim of the present project is to establish an enantioselective total synthesis of curvicollide C, a polyketide isolated from the mycoparasitic fungi Podospora curvicolla. Our extensive exploratory efforts have culminated into the credible research proposal at hand which defines important and interesting scientific questions.The isolation and structural elucidation of the C26-curvicollides A-C was first reported by Gloer et al. in 2004.The relative configuration of the polyketide was only partially elucidated and the absolute configuration remains unknown. Our project is aimed at the elucidation of the absolute configuration of curvicollide C by total synthesis of diastereomers of the natural product and their characterization by chiroptical methods. Furthermore, since it has been reported that curvicollide A shows promising antifungal activities but curvicollide C could not be tested due to lack of material, providing access to the natural product and derivatives thereof would enable a comprehensive biological study. The unique constitution of the curvicollides implicates a rather unusual biosynthetic pathway in which the carbon backbone of the curvicollides is assembled by the condensation of a hexa- and a pentaketide to establish the characteristic central lactone moiety. The projected synthesis of the lactone with the two attached 1,3-diene segments defines one of the central scientific challenges which we hope to resolve relying on a highly modular synthetic strategy. Because the curvicollides A-C are only distinguished by the substituent pattern in the eastern part of the molecule, a successful modular synthesis of curvicollide C should enable the synthesis of the other members of this family of polykketides.

阐明天然产物的构型和为生物学研究提供的衍生品是非常重要的。在这方面，本项目的目的是建立一种从真菌Podospora curvicolla中分离出来的聚酮类化合物Curvicollide C的对映选择性全合成方法。我们广泛的探索努力最终形成了手头可信的研究提案，它定义了重要和有趣的科学问题。C26-Curvicollides A-C的分离和结构鉴定首先由Gloer等人报道。2004年，聚酮的相对构型仅被部分阐明，绝对构型尚不清楚。本项目旨在通过天然产物的非对映异构体的全合成和手性方法对其进行表征，以阐明其绝对构型。此外，由于已有报道表明，曲线内酯A显示出良好的抗真菌活性，但由于缺乏材料，无法对曲线内酯C进行测试，因此，提供获得天然产物及其衍生物的途径将使全面的生物学研究成为可能。曲内酯的独特组成暗示了一种相当不寻常的生物合成途径，其中曲内酯的碳骨架由六酮和五酮缩合而成，建立了特征的中心内酯部分。内酯与两个连接的1，3-二烯链段的计划合成定义了中心科学挑战之一，我们希望依靠高度模块化的合成策略来解决这一挑战。由于曲内酯A-C只通过分子东部的取代基模式来区分，所以成功的曲内酯C的模块化合成应该能够合成这个聚酮家族的其他成员。