We report an efficient and convergent strategy for the total synthesis of UCS1025A and its diastereomer tetra-epi-UCS1025A.Ucs1025A is a representative member of the naturally occurring pyrrolizidinone polyketides,fro...We report an efficient and convergent strategy for the total synthesis of UCS1025A and its diastereomer tetra-epi-UCS1025A.Ucs1025A is a representative member of the naturally occurring pyrrolizidinone polyketides,from which members with potent antibacterial,antifungal,and anticancer activities have been identified.Our approach features a tandem carbonylative Stille cross coupling and Diels-Alder reaction to forge a key C-C bond and build the trans-decalin system.This tandem process utilizes carbon monoxide as a one-carbon linchpin to stitch a vinyl triflate and a vinylstannane together and form the desired enone moiety for the subsequent intramolecular Diels-Alder cyclization.Our synthesis also provides a versatile approach for the synthesis of other related pyrrolizidinone-containing polyketides.展开更多
Microbial cell factories(MCFs)and cell-free systems(CFSs)are generally considered as two unrelated approaches for the biosynthesis of biomolecules.In the current study,two systems were combined together for the overpr...Microbial cell factories(MCFs)and cell-free systems(CFSs)are generally considered as two unrelated approaches for the biosynthesis of biomolecules.In the current study,two systems were combined together for the overproduction of agroclavine(AC),a structurally complex ergot alkaloid.The whole biosynthetic pathway for AC was split into the early pathway and the late pathway at the point of the FAD-linked oxidoreductase EasE,which was reconstituted in an MCF(Aspergillus nidulans)and a four-enzyme CFS,respectively.The final titer of AC of this combined system is 1209 mg/L,which is the highest one that has been reported so far,to the best of our knowledge.The development of such a combined route could potentially avoid the limitations of both MCF and CFS systems,and boost the production of complex ergot alkaloids with polycyclic ring systems.展开更多
文摘We report an efficient and convergent strategy for the total synthesis of UCS1025A and its diastereomer tetra-epi-UCS1025A.Ucs1025A is a representative member of the naturally occurring pyrrolizidinone polyketides,from which members with potent antibacterial,antifungal,and anticancer activities have been identified.Our approach features a tandem carbonylative Stille cross coupling and Diels-Alder reaction to forge a key C-C bond and build the trans-decalin system.This tandem process utilizes carbon monoxide as a one-carbon linchpin to stitch a vinyl triflate and a vinylstannane together and form the desired enone moiety for the subsequent intramolecular Diels-Alder cyclization.Our synthesis also provides a versatile approach for the synthesis of other related pyrrolizidinone-containing polyketides.
基金This study was supported by the National Key Research and Development Program of China(grant nos.2021YFC2100600,2019YFA0905100 and 2018YFA0901600)the National Natural Science Foundation of China(grant nos.31872614,32022002,21977113)+1 种基金the Youth Scientists Innovation Promotion Association of CAS(2019090)to S.S.G.,Innovative Cross Team project of Chinese Academy of Sciences,CAS(grant no.JCTD-2019-06)Shandong Provincial Natural Science Foundation(Major Basic Research Projects)(grant no.ZR2019ZD18).
文摘Microbial cell factories(MCFs)and cell-free systems(CFSs)are generally considered as two unrelated approaches for the biosynthesis of biomolecules.In the current study,two systems were combined together for the overproduction of agroclavine(AC),a structurally complex ergot alkaloid.The whole biosynthetic pathway for AC was split into the early pathway and the late pathway at the point of the FAD-linked oxidoreductase EasE,which was reconstituted in an MCF(Aspergillus nidulans)and a four-enzyme CFS,respectively.The final titer of AC of this combined system is 1209 mg/L,which is the highest one that has been reported so far,to the best of our knowledge.The development of such a combined route could potentially avoid the limitations of both MCF and CFS systems,and boost the production of complex ergot alkaloids with polycyclic ring systems.
