Diastereodivergent Construction of Octahydrophenanthridinone and Octahydrophenanthridine Cores

Diastereodivergent synthesis of octahydrophenanthridinone and octahydrophenanthridine skeletons, structural motifs often found in biologically active natural products, is described. We previously reported a total synthesis of a pancratistatin analog using novel octahydrophenanthridinone construction...

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Main Authors: Chunzhao Sun, Hiromichi Nishikawa, Tsubasa Inokuma, Ken-ichi Yamada
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/2/371
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author Chunzhao Sun
Hiromichi Nishikawa
Tsubasa Inokuma
Ken-ichi Yamada
author_facet Chunzhao Sun
Hiromichi Nishikawa
Tsubasa Inokuma
Ken-ichi Yamada
author_sort Chunzhao Sun
collection DOAJ
description Diastereodivergent synthesis of octahydrophenanthridinone and octahydrophenanthridine skeletons, structural motifs often found in biologically active natural products, is described. We previously reported a total synthesis of a pancratistatin analog using novel octahydrophenanthridinone construction. In this study, we examined the generality of our method and its extension to octahydrophenanthridine formation. Conjugate addition of diarylcuprates to nitrosocyclohexenes, which were generated in situ from 2-chlorocyclohexanone oximes, provided 2-arylcyclohexanone oximes. Subsequent reduction of the oxime moiety gave <i>cis</i>- and <i>trans</i>-configured amines. Both amines were separately converted into the corresponding octahydrophenanthridinones and octahydrophenanthridines via hexahydrophenanthridine intermediates.
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institution Kabale University
issn 1420-3049
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publishDate 2025-01-01
publisher MDPI AG
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series Molecules
spelling doaj-art-38e7016753744fb4b932a6be1a19a20f2025-01-24T13:43:48ZengMDPI AGMolecules1420-30492025-01-0130237110.3390/molecules30020371Diastereodivergent Construction of Octahydrophenanthridinone and Octahydrophenanthridine CoresChunzhao Sun0Hiromichi Nishikawa1Tsubasa Inokuma2Ken-ichi Yamada3Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi 770-8505, Tokushima, JapanGraduate School of Pharmaceutical Sciences, Tokushima University, Shomachi 770-8505, Tokushima, JapanGraduate School of Pharmaceutical Sciences, Tokushima University, Shomachi 770-8505, Tokushima, JapanGraduate School of Pharmaceutical Sciences, Tokushima University, Shomachi 770-8505, Tokushima, JapanDiastereodivergent synthesis of octahydrophenanthridinone and octahydrophenanthridine skeletons, structural motifs often found in biologically active natural products, is described. We previously reported a total synthesis of a pancratistatin analog using novel octahydrophenanthridinone construction. In this study, we examined the generality of our method and its extension to octahydrophenanthridine formation. Conjugate addition of diarylcuprates to nitrosocyclohexenes, which were generated in situ from 2-chlorocyclohexanone oximes, provided 2-arylcyclohexanone oximes. Subsequent reduction of the oxime moiety gave <i>cis</i>- and <i>trans</i>-configured amines. Both amines were separately converted into the corresponding octahydrophenanthridinones and octahydrophenanthridines via hexahydrophenanthridine intermediates.https://www.mdpi.com/1420-3049/30/2/371octahydrophenanthridinoneoctahydrophenanthridinealkaloidstereodivergent synthesisarylationorganocuprate
spellingShingle Chunzhao Sun
Hiromichi Nishikawa
Tsubasa Inokuma
Ken-ichi Yamada
Diastereodivergent Construction of Octahydrophenanthridinone and Octahydrophenanthridine Cores
Molecules
octahydrophenanthridinone
octahydrophenanthridine
alkaloid
stereodivergent synthesis
arylation
organocuprate
title Diastereodivergent Construction of Octahydrophenanthridinone and Octahydrophenanthridine Cores
title_full Diastereodivergent Construction of Octahydrophenanthridinone and Octahydrophenanthridine Cores
title_fullStr Diastereodivergent Construction of Octahydrophenanthridinone and Octahydrophenanthridine Cores
title_full_unstemmed Diastereodivergent Construction of Octahydrophenanthridinone and Octahydrophenanthridine Cores
title_short Diastereodivergent Construction of Octahydrophenanthridinone and Octahydrophenanthridine Cores
title_sort diastereodivergent construction of octahydrophenanthridinone and octahydrophenanthridine cores
topic octahydrophenanthridinone
octahydrophenanthridine
alkaloid
stereodivergent synthesis
arylation
organocuprate
url https://www.mdpi.com/1420-3049/30/2/371
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AT tsubasainokuma diastereodivergentconstructionofoctahydrophenanthridinoneandoctahydrophenanthridinecores
AT kenichiyamada diastereodivergentconstructionofoctahydrophenanthridinoneandoctahydrophenanthridinecores