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Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products

Triterpenoid natural products from the Schisandraceae family have long presented a significant synthetic challenge. Lancifodilactone I, a member of the family not previously synthesized, was identified as a key natural product target, from which many other members could be synthesized. We envisaged...

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Autores principales: Kravljanac, Pavle, Anderson, Edward A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254518/
https://www.ncbi.nlm.nih.gov/pubmed/37298943
http://dx.doi.org/10.3390/molecules28114468
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author Kravljanac, Pavle
Anderson, Edward A.
author_facet Kravljanac, Pavle
Anderson, Edward A.
author_sort Kravljanac, Pavle
collection PubMed
description Triterpenoid natural products from the Schisandraceae family have long presented a significant synthetic challenge. Lancifodilactone I, a member of the family not previously synthesized, was identified as a key natural product target, from which many other members could be synthesized. We envisaged that the core ring system of lancifodilactone I could be accessed by a strategy involving palladium-catalysed cascade cyclisation of a bromoenynamide, via carbopalladation, Suzuki coupling and 8π-electrocyclisation, to synthesize the core 7,8-fused ring system. Exploration of this strategy on model systems resulted in efficient syntheses of 5,6- and 5,8-fused systems in high yields, which represent the first such cyclisation where the ynamide nitrogen atom is ‘external’ to the forming ring system. The enamide functionality resident in the cascade cyclisation product was found to be less nucleophilic than the accompanying tri-/tetrasubstituted alkene(s), enabling regioselective oxidations. Application of this strategy to 7,6-, and 7,8-fused systems, and ultimately the ‘real’ substrate, was ultimately thwarted by the difficulty of 7-membered ring closure, leading to side product formation. Nevertheless, a tandem bromoenynamide carbopalladation, Suzuki coupling and 6/8π-electrocyclisation was shown to be a highly efficient tactic for the formation of bicyclic enamides, which may find applications in other synthetic contexts.
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spelling pubmed-102545182023-06-10 Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products Kravljanac, Pavle Anderson, Edward A. Molecules Article Triterpenoid natural products from the Schisandraceae family have long presented a significant synthetic challenge. Lancifodilactone I, a member of the family not previously synthesized, was identified as a key natural product target, from which many other members could be synthesized. We envisaged that the core ring system of lancifodilactone I could be accessed by a strategy involving palladium-catalysed cascade cyclisation of a bromoenynamide, via carbopalladation, Suzuki coupling and 8π-electrocyclisation, to synthesize the core 7,8-fused ring system. Exploration of this strategy on model systems resulted in efficient syntheses of 5,6- and 5,8-fused systems in high yields, which represent the first such cyclisation where the ynamide nitrogen atom is ‘external’ to the forming ring system. The enamide functionality resident in the cascade cyclisation product was found to be less nucleophilic than the accompanying tri-/tetrasubstituted alkene(s), enabling regioselective oxidations. Application of this strategy to 7,6-, and 7,8-fused systems, and ultimately the ‘real’ substrate, was ultimately thwarted by the difficulty of 7-membered ring closure, leading to side product formation. Nevertheless, a tandem bromoenynamide carbopalladation, Suzuki coupling and 6/8π-electrocyclisation was shown to be a highly efficient tactic for the formation of bicyclic enamides, which may find applications in other synthetic contexts. MDPI 2023-05-31 /pmc/articles/PMC10254518/ /pubmed/37298943 http://dx.doi.org/10.3390/molecules28114468 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kravljanac, Pavle
Anderson, Edward A.
Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products
title Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products
title_full Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products
title_fullStr Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products
title_full_unstemmed Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products
title_short Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products
title_sort synthetic study toward triterpenes from the schisandraceae family of natural products
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254518/
https://www.ncbi.nlm.nih.gov/pubmed/37298943
http://dx.doi.org/10.3390/molecules28114468
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