Total Synthesis of Curvicollid C

天然产物构型的阐明和生物学研究所需衍生物的供应是极其重要的。在这方面，本项目的目的是建立一个对映选择性的全合成curvicollide C，一个聚酮分离的真菌Podospora curvicolla。2004年，Gloer等首次报道了C26-curvicollides A-C的分离和结构鉴定，并对聚酮化合物的相对构型进行了部分鉴定，其绝对构型仍未知。本课题旨在通过天然产物的非对映异构体的全合成及其手性光学方法的表征来阐明Curvicollide C的绝对构型。此外，由于已经报道了curvicollide A显示出有希望的抗真菌活性，但是curvicollide C由于缺乏材料而不能被测试，因此提供获得天然产物及其衍生物的途径将使得能够进行全面的生物学研究。curvicollides的独特构造暗示了一种相当不寻常的生物合成途径，其中curvicollides的碳骨架通过六肽和pentaketide的缩合来组装，以建立特征性的中心内酯部分。计划合成的内酯与两个连接的1，3-二烯段定义了一个中心的科学挑战，我们希望解决依赖于一个高度模块化的合成策略。因为curvicollide A-C仅通过分子东部的取代基模式来区分，所以curvicollide C的成功的模块化合成应该能够合成该聚酮化合物家族的其他成员。

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.