Natural products with diverse functional groups and stereo-genic centers have inspired therapeutics and underpin the modern drug discovery process.Their three-dimensional molecular structures need to be unambiguously ...Natural products with diverse functional groups and stereo-genic centers have inspired therapeutics and underpin the modern drug discovery process.Their three-dimensional molecular structures need to be unambiguously determined in order to be realized as clinical candidates or to achieve further activity-guided structural optimization.Although recent advances in spectroscopic methods have made it possible for researchers to determine the structures of microgram samples of complex natural products,there is no universally accepted method for determining the relative and absolute configuration of a naturally occurring compound.We report the determination of the full stereostructure of valactamide A,an eight-stereogenic-center-containing fungal metabolite by the synergy of prediction rule-guided analysis and chemical synthesis.The expedient total synthesis resulted in unambiguous verification of the predicted stereochemistry for valactamide A.展开更多
基金This research was funded by the 2022 Shenzhen Sustainable Supporting Funds for Colleges and Universities(No.20220811103834002)the Guangdong Basic and Applied Basic Research Foundation(2022A1515110592 and 2023A1515012715)+3 种基金the Technology&Innovation Bureau of Longgang District(RCTDPT-2019−008)the Guangdong Natural Science Foundation(2021A1515010344)the Guang-dong Department of Education(2021ZDJS097)the National Natural Science Foundation of China(22171014,21901013,32370069).This work was inspired by the international and interdisciplinary environments of the JSPS Asian CORE Program,“Asian Chemical Biology Initiative.”。
文摘Natural products with diverse functional groups and stereo-genic centers have inspired therapeutics and underpin the modern drug discovery process.Their three-dimensional molecular structures need to be unambiguously determined in order to be realized as clinical candidates or to achieve further activity-guided structural optimization.Although recent advances in spectroscopic methods have made it possible for researchers to determine the structures of microgram samples of complex natural products,there is no universally accepted method for determining the relative and absolute configuration of a naturally occurring compound.We report the determination of the full stereostructure of valactamide A,an eight-stereogenic-center-containing fungal metabolite by the synergy of prediction rule-guided analysis and chemical synthesis.The expedient total synthesis resulted in unambiguous verification of the predicted stereochemistry for valactamide A.
