Total synthesis of (±)-17-norcamptothecin, a novel E-ring modified camptothecin

Devert, Marie; Sabot, Cyrille; Giboreau, Pascale; Constant, Jean‐François; Greene, Andrew E.; Kanazawa, Alice

doi:10.1016/j.tet.2010.06.003

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…An interesting example was the synthesis of norcamptothecin including an -hydroxy--lactone E-ring, starting from bicyclic hydroxy-2-pyridone P-36 (Scheme 61). 106 The key step of these transformations was the Claisen rearrangement of P-83 providing pyridone P-84. Acetylcholinesterase (AChE) is the key brain enzyme, responsible for the rapid degradation of neurotransmitter acetylcholine, which is observed to take place in Alzheimer's type diseases.…”

Section: Scheme 57 Multicomponent Synthesis Of Catharanthine Analoguesmentioning

confidence: 99%

Pyridones – Powerful Precursors for the Synthesis of Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds

Sośnicki¹,

Idzik²

2019

Synthesis

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2-Pyridone is characterized by a very wide range of reactivity of a different nature, ranging from electrophilic aromatic substitution, CH–metal-mediated reactions, and NH/OH functionalization of both possible lactam/lactim tautomers, through cycloaddition, to nucleophilic addition and transformation of the tautomeric C=O/C–OH moiety. The high availability of 2-pyridones and the possibility of their far-reaching functionalization additionally increased their values. Therefore, they are very useful building blocks for the synthesis of structurally diverse piperidine and pyridine compounds, including naturally occurring 2-pyridones. This review reports on the use of simple 2-pyridones in the synthesis of alkaloids and alkaloids-inspired compounds based on the piperidine or pyridine framework.1 Introduction2 Structure, Availability, and Reactivity of 2-Pyridones3 Monocyclic Piperidine Alkaloids from 2-Pyridones4 Polycyclic Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds from 2-Pyridones4.1 New Ring Formation Involving C/N Atoms of the 2-Pyridone Ring4.1.1 Indolizine-Fused 2-Pyridones: Camptothecins and Related Compounds4.1.2 Other Indolizines from 2-Pyridones4.1.3 Compounds Bearing the Quinolizine Ring System4.2 New Ring Formation Involving C/C Atoms of the 2-Pyridone Ring4.2.1 C-2/C-3 Ring Fusion4.2.2 C-3/C-4 Ring Fusion4.2.3 C-4/C-5 Ring Fusion4.2.4 C-5/C-6 Ring Fusion4.2.5 C-2/C-4 Ring Bridge4.2.6 C-2/C-6 Ring Bridge4.2.7 C-3/C-5 Ring Bridge4.2.8 C-3/C-6 Ring Bridge4.2.9 C-4/C-6 Ring Bridge5 Conclusion

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Section: Scheme 57 Multicomponent Synthesis Of Catharanthine Analoguesmentioning

confidence: 99%

Pyridones – Powerful Precursors for the Synthesis of Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds

Sośnicki¹,

Idzik²

2019

Synthesis

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“…[1][2][3][4][5][6][7] Further, a significant number of compounds with a 2(1H)-pyridinone motif exhibit interesting activities against a number of biological targets, and are used as scaffolds in drug discovery. [8][9][10][11] Methods for 2(1H)-pyridinone ring formation can be based on bi-and multicomponent reactions, intramolecular cyclizations and transformation of other hyterocycles.…”

Section: Introductionmentioning

confidence: 99%

Intramolecular cyclization of N-(3-oxoalkenyl)phenylacetamides: synthesis of 3-phenyl-2(1H)-pyridones

Goncharov¹,

Garkushenko²,

Savelieva³

et al. 2015

Arkivoc

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3-Phenyl-2(1Н)-pyridinones were obtained by base-catalyzed intramolecular aldol-type cyclization of N-(3-oxoalkenyl)phenylacetamides. The effect of substituents in the starting compounds and the experimental conditions on the reaction course were established. It was shown that the transformations of N-(3-oxoalkenyl)amides in basic medium depend on structural and electronic factors as well as the reaction conditions.

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“…Although most CPT derivatives exhibit a natural and strong blue fluorescence, their absorption and emission spectra (e.g., shape, intensity, and wavelength) are highly dependent on the analogue considered and the stability of their crucial E-ring lactone. Indeed, under physiological conditions, the lactone ring of CPT is rapidly hydrolyzed into the usually less fluorescent and physiologically active carboxylate form. − Even if the intrinsic fluorescence properties of CPT could be compatible with in vitro bioassays, more challenging bioanalytical applications focusing on the tracking of biological events (following administration of this bioactive compound) in cellulo or in vivo could not be easily implemented due to the blue light absorption and scattering by the biological matrix and the background signal from cellular autofluorescence . Thus, it is essential to dispose of a reliable fluorescent chemical reporter conveniently link to the bioactive alkaloid, to efficiently track the biological processes, whatever the analogues considered and the proportion of its lactone form in biological media.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Evaluation, and in Vivo Imaging of the first Camptothecin–Fluorescein Conjugate

et al. 2013

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The first synthesis and photophysical properties of a fluorecently labeled camptothecin derivative, namely, camptothecin-FI (CPT-FI), an antitumoral agent that targets topoisomerase I, are reported. The preparation of this fluorescent conjugate is based on a highly convergent and flexible approach which enables the rapid chemical modification of the AB ring system of this fragile pentacyclic alkaloid, aimed at introducing an anchoring point to graft the fluorophore. The selection of a fluorescein analogue as the reporter group has enabled us to get the first green-emitting CPT conjugate exhibiting valuable spectral properties and retaining biological properties of native CPT. Indeed, in biological models, i.e., glioma cell lines U87 and/or T98, the kinetics of cell endocytosis, as well as the efficacy of CPT-FI were compared to those of CPT. CPT-FI fluorescence was measured in the cytosolic compartment of T98 glioma cells from 5 min treatment and remained detectable until 48 h. As CPT, CPT-FI drastically inhibited glioma growth and cell cycle but exhibited a reduced affinity as compared to the native CPT. In vivo and ex vivo imaging studies of CPT-FI intratumoraly injected into a model of NIH-3T3 murine tumor xenografts in nude mice, showed accumulation around the injected site area, which is very promising to target tumors and follow biodistribution in vivo.

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Total synthesis of (±)-17-norcamptothecin, a novel E-ring modified camptothecin

Cited by 6 publications

References 43 publications

Pyridones – Powerful Precursors for the Synthesis of Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds

Pyridones – Powerful Precursors for the Synthesis of Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds

Intramolecular cyclization of N-(3-oxoalkenyl)phenylacetamides: synthesis of 3-phenyl-2(1H)-pyridones

Synthesis, Biological Evaluation, and in Vivo Imaging of the first Camptothecin–Fluorescein Conjugate

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