Total syntheses of the parvistemoline alkaloids enabled by stereocontrolled Ir/Pd-catalyzed allylic alkylation
Abstract The functionalized polycycle with densely contiguous tertiary stereocenters is a formidable challenge in synthesizing the parvistemoline family of Stemona alkaloids. We herein report their catalytic, asymmetric total syntheses in 13–14 steps from commercially available 2-(methoxycarbonyl)-p...
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2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55111-2 |
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| author | Xiao Liang Qian-Hui Ding Jian-Ting Yang Hua-Fei Yang Yi Deng Li Shi Kun Wei Yu-Rong Yang |
| author_facet | Xiao Liang Qian-Hui Ding Jian-Ting Yang Hua-Fei Yang Yi Deng Li Shi Kun Wei Yu-Rong Yang |
| author_sort | Xiao Liang |
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| description | Abstract The functionalized polycycle with densely contiguous tertiary stereocenters is a formidable challenge in synthesizing the parvistemoline family of Stemona alkaloids. We herein report their catalytic, asymmetric total syntheses in 13–14 steps from commercially available 2-(methoxycarbonyl)-pyrrole, featuring the development and deployment of an Ir/Pd-synergistically-catalyzed allylation of α-non-substituted keto esters with secondary aryl-substituted alcohols, stereodivergently accessible to four stereoisomers. Using chiral Pd-enolate and Ir π-allyl complex under neutral conditions, no epimerization occurs. Additionally, the other two adjacent stereogenic centers can be installed diastereoselectively by Zn(BH4)2-promoted reduction and Krische’s Ir-catalyzed 2-(alkoxycarbonyl)allylation. Oxy-Michael addition delivered the fused tetrahydrofuran-γ-lactone scaffold. At the later stage, hydrogenation or oxidation of pyrrole moiety furnished groups of tetrahydropyrrole and pyrrolidone. Finally, vinylogous Mannich reaction of an in situ generated iminium ion or Krische’s Ir-catalyzed 2-(alkoxycarbonyl)allylation of aldehyde installed the monocyclic lactone for parvistemonine (2) and didehydroparvistemonine (3), respectively. |
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| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-dbb29e762fd7451ab2df1d2b93e4cda92025-01-05T12:36:10ZengNature PortfolioNature Communications2041-17232024-12-0115111110.1038/s41467-024-55111-2Total syntheses of the parvistemoline alkaloids enabled by stereocontrolled Ir/Pd-catalyzed allylic alkylationXiao Liang0Qian-Hui Ding1Jian-Ting Yang2Hua-Fei Yang3Yi Deng4Li Shi5Kun Wei6Yu-Rong Yang7Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesKey Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesKey Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesKey Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesKey Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesKey Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesKey Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesKey Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of SciencesAbstract The functionalized polycycle with densely contiguous tertiary stereocenters is a formidable challenge in synthesizing the parvistemoline family of Stemona alkaloids. We herein report their catalytic, asymmetric total syntheses in 13–14 steps from commercially available 2-(methoxycarbonyl)-pyrrole, featuring the development and deployment of an Ir/Pd-synergistically-catalyzed allylation of α-non-substituted keto esters with secondary aryl-substituted alcohols, stereodivergently accessible to four stereoisomers. Using chiral Pd-enolate and Ir π-allyl complex under neutral conditions, no epimerization occurs. Additionally, the other two adjacent stereogenic centers can be installed diastereoselectively by Zn(BH4)2-promoted reduction and Krische’s Ir-catalyzed 2-(alkoxycarbonyl)allylation. Oxy-Michael addition delivered the fused tetrahydrofuran-γ-lactone scaffold. At the later stage, hydrogenation or oxidation of pyrrole moiety furnished groups of tetrahydropyrrole and pyrrolidone. Finally, vinylogous Mannich reaction of an in situ generated iminium ion or Krische’s Ir-catalyzed 2-(alkoxycarbonyl)allylation of aldehyde installed the monocyclic lactone for parvistemonine (2) and didehydroparvistemonine (3), respectively.https://doi.org/10.1038/s41467-024-55111-2 |
| spellingShingle | Xiao Liang Qian-Hui Ding Jian-Ting Yang Hua-Fei Yang Yi Deng Li Shi Kun Wei Yu-Rong Yang Total syntheses of the parvistemoline alkaloids enabled by stereocontrolled Ir/Pd-catalyzed allylic alkylation Nature Communications |
| title | Total syntheses of the parvistemoline alkaloids enabled by stereocontrolled Ir/Pd-catalyzed allylic alkylation |
| title_full | Total syntheses of the parvistemoline alkaloids enabled by stereocontrolled Ir/Pd-catalyzed allylic alkylation |
| title_fullStr | Total syntheses of the parvistemoline alkaloids enabled by stereocontrolled Ir/Pd-catalyzed allylic alkylation |
| title_full_unstemmed | Total syntheses of the parvistemoline alkaloids enabled by stereocontrolled Ir/Pd-catalyzed allylic alkylation |
| title_short | Total syntheses of the parvistemoline alkaloids enabled by stereocontrolled Ir/Pd-catalyzed allylic alkylation |
| title_sort | total syntheses of the parvistemoline alkaloids enabled by stereocontrolled ir pd catalyzed allylic alkylation |
| url | https://doi.org/10.1038/s41467-024-55111-2 |
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