Straightforward Access to the Dispirocyclic Framework via Regioselective Intramolecular Michael Addition

In this article, an efficient and straightforward protocol for the construction of complex dispirocyclic skeletons via regioselective intramolecular Michael addition is presented. Diverse dispirocyclic compounds were synthesized under mild and transition-metal-free conditions with good to excellent...

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Main Authors: Weilun Cao, Junmin Dong, Xuan Pan, Zhanzhu Liu
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/15/3164
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author Weilun Cao
Junmin Dong
Xuan Pan
Zhanzhu Liu
author_facet Weilun Cao
Junmin Dong
Xuan Pan
Zhanzhu Liu
author_sort Weilun Cao
collection DOAJ
description In this article, an efficient and straightforward protocol for the construction of complex dispirocyclic skeletons via regioselective intramolecular Michael addition is presented. Diverse dispirocyclic compounds were synthesized under mild and transition-metal-free conditions with good to excellent yields. Most stereoisomers were conveniently separated by column chromatography, and their relative configurations were identified by single-crystal X-Ray diffraction of representative compounds. A scale-up experiment validated the practicality of this method. In an in vitro assay, some dispirocyclic compounds exhibited potent cytotoxicity with an IC<sub>50</sub> value of 10<sup>−6</sup> mol/L.
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series Molecules
spelling doaj-art-5fefbb911b3b4ae992ad04e311a0c3b82025-08-20T03:02:49ZengMDPI AGMolecules1420-30492025-07-013015316410.3390/molecules30153164Straightforward Access to the Dispirocyclic Framework via Regioselective Intramolecular Michael AdditionWeilun Cao0Junmin Dong1Xuan Pan2Zhanzhu Liu3State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, ChinaIn this article, an efficient and straightforward protocol for the construction of complex dispirocyclic skeletons via regioselective intramolecular Michael addition is presented. Diverse dispirocyclic compounds were synthesized under mild and transition-metal-free conditions with good to excellent yields. Most stereoisomers were conveniently separated by column chromatography, and their relative configurations were identified by single-crystal X-Ray diffraction of representative compounds. A scale-up experiment validated the practicality of this method. In an in vitro assay, some dispirocyclic compounds exhibited potent cytotoxicity with an IC<sub>50</sub> value of 10<sup>−6</sup> mol/L.https://www.mdpi.com/1420-3049/30/15/3164spiro compoundsregioselectivitytransition-metal free
spellingShingle Weilun Cao
Junmin Dong
Xuan Pan
Zhanzhu Liu
Straightforward Access to the Dispirocyclic Framework via Regioselective Intramolecular Michael Addition
Molecules
spiro compounds
regioselectivity
transition-metal free
title Straightforward Access to the Dispirocyclic Framework via Regioselective Intramolecular Michael Addition
title_full Straightforward Access to the Dispirocyclic Framework via Regioselective Intramolecular Michael Addition
title_fullStr Straightforward Access to the Dispirocyclic Framework via Regioselective Intramolecular Michael Addition
title_full_unstemmed Straightforward Access to the Dispirocyclic Framework via Regioselective Intramolecular Michael Addition
title_short Straightforward Access to the Dispirocyclic Framework via Regioselective Intramolecular Michael Addition
title_sort straightforward access to the dispirocyclic framework via regioselective intramolecular michael addition
topic spiro compounds
regioselectivity
transition-metal free
url https://www.mdpi.com/1420-3049/30/15/3164
work_keys_str_mv AT weiluncao straightforwardaccesstothedispirocyclicframeworkviaregioselectiveintramolecularmichaeladdition
AT junmindong straightforwardaccesstothedispirocyclicframeworkviaregioselectiveintramolecularmichaeladdition
AT xuanpan straightforwardaccesstothedispirocyclicframeworkviaregioselectiveintramolecularmichaeladdition
AT zhanzhuliu straightforwardaccesstothedispirocyclicframeworkviaregioselectiveintramolecularmichaeladdition