Total Synthesis of Curvicollid C

阐明天然产物的结构和为生物学研究提供衍生物是至关重要的。在这方面，本项目的目的是建立一个对映选择性全合成curvicollide C，一种从曲枝真菌Podospora curvicolla中分离的聚酮。我们广泛的探索努力最终形成了可信的研究建议，其中定义了重要而有趣的科学问题。Gloer等人于2004年首次报道了C26-curvicollides A-C的分离和结构解析。聚酮的相对构型只被部分阐明，绝对构型仍然未知。我们的项目旨在通过天然产物的非对映体的全合成来阐明曲线碰撞体C的绝对构型，并通过热学方法对其进行表征。此外，由于有报道称curvicollide A具有良好的抗真菌活性，而curvicollide C由于缺乏材料而无法进行测试，因此提供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。曲曲内酯的独特结构暗示了一种相当不寻常的生物合成途径，其中曲曲内酯的碳主链是通过一个六肽和一个五肽的缩合来组装的，以建立特征的中心内酯部分。内酯与两个连接的1,3-二烯段的预计合成定义了我们希望依靠高度模块化的合成策略来解决的核心科学挑战之一。由于曲曲内酯a -C仅通过分子东部的取代基模式来区分，因此成功的模合成曲曲内酯C应该能够合成该聚酮家族的其他成员。

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.