Synthesis of spirocyclopropyl γ-lactams by tandem intramolecular azetidine ring-opening/closing cascade reaction: synthetic and mechanistic aspects

Nocquet, Pierre‐Antoine; Hazelard, Damien; Compain, Philippe

doi:10.1016/j.tet.2012.03.111

Cited by 22 publications

(8 citation statements)

References 52 publications

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“…Moreover, the cyclopropane motif is found in many natural products and has attracted special attention for its pharmacological activities . In addition, the cyclopropyl scaffold is a useful tool for the design of constrained bioactive molecules that project pharmacophore into the appropriate protein binding pockets. , Thus, we report the synthesis of parthenolide and its hitherto unreported cyclopropyl analogue (compound 10 ).…”

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confidence: 99%

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Protection-Group-Free Semisyntheses of Parthenolide and Its Cyclopropyl Analogue

Long

Ding²,

Wang

et al. 2013

J. Org. Chem.

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Parthenolide showed extensive bioactivities including selective eradication of AML stem cells. Herein we report protection-free semisyntheses of parthenolide and its cyclopropyl analogue (compound 10) from the abundant natural product costunolide with an overall yield of 55 and 60%, respectively. Compound 10 was more stable than parthenolide, and it maintained comparable activities against AML cell lines and AML stem cells. Therefore, compound 10 might be a superior small molecule than parthenolide as a tool for investigation of cancer stem cell biology.

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confidence: 99%

“…11 In addition, the cyclopropyl scaffold is a useful tool for the design of constrained bioactive molecules that project pharmacophore into the appropriate protein binding pockets. 12,13 Thus, we report the synthesis of parthenolide and its hitherto unreported cyclopropyl analogue (compound 10).…”

mentioning

confidence: 99%

Protection-Group-Free Semisyntheses of Parthenolide and Its Cyclopropyl Analogue

Long

Ding²,

Wang

et al. 2013

J. Org. Chem.

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“…Therefore, we hypothesized that the replacement of the unconjugated exo -double bonds with potentially bioisosteric cyclopropyl moieties might provide a novel class of stable spirocyclopropyl dehydrocostus lactone analogs. Moreover, the cyclopropane motif is found in many natural products, and this three-membered structure has recently attracted special attention for the appealing structure and their pharmacological interests [43]; the spirocyclopropyl scaffold is indeed a useful tool for the design of constrained bioactive molecules that project pharmacophores into the appropriate protein binding pockets [44,45]. Compound 7 is bench-stable in the solid state.…”

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confidence: 99%

Sesquiterpene Lactones and Their Derivatives Inhibit High Glucose-Induced NF-κB Activation and MCP-1 and TGF-β1 Expression in Rat Mesangial Cells

et al. 2013

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Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-β1 gene expression, western blot to detect the level of IκBα protein and EMSA to measure the activation of nuclear factor kappa B (NF-κB). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-κB, the degradation of IκBα, and the expression of MCP-1, TGF-β1 and

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“…Further, treatment of 204 with NaH in THF resulted in the synthesis of tetrahydropyrimidinones, 205 and 206 as a 6 : 4 epimeric mixture (Scheme 48). 56 Compain and co-workers 57 have developed the route for the synthesis of spirocyclopropyl g-lactams via tandem intramolecular azetidine ring-opening/closing cascade reaction. The key step involved the SN 2 -type ring-opening of TMSOTfactivated azetidine ring by silyl ketene acetals.…”

Section: Azetidines As Versatile Synthonsmentioning

confidence: 99%

Recent advances in synthetic facets of immensely reactive azetidines

et al. 2017

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Synthesis of spirocyclopropyl γ-lactams by tandem intramolecular azetidine ring-opening/closing cascade reaction: synthetic and mechanistic aspects

Cited by 22 publications

References 52 publications

Protection-Group-Free Semisyntheses of Parthenolide and Its Cyclopropyl Analogue

Protection-Group-Free Semisyntheses of Parthenolide and Its Cyclopropyl Analogue

Sesquiterpene Lactones and Their Derivatives Inhibit High Glucose-Induced NF-κB Activation and MCP-1 and TGF-β1 Expression in Rat Mesangial Cells

Recent advances in synthetic facets of immensely reactive azetidines

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