Diastereoselective Multicomponent Synthesis of Dihydropyridones with an Isocyanide Functionality

Paravidino, Monica; Bon, Robin S.; Scheffelaar, Rachel; Vugts, Daniëlle J.; Znabet, Anass; Schmitz, Rob F.; Kanter, Frans J. J. de; Lutz, Martin; Spek, Anthony L.; Groen, Marinus B.; Orru, Romano V. A.

doi:10.1021/ol062204b

Cited by 49 publications

(37 citation statements)

References 26 publications

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“…[53] Perhaps the most intriguing reaction in this family is the reaction of azadiene 54 with a-isocyano esters to give isocyano-substituted dihydropyridones 67. [54,55] The retained isocyanide function allows combination with isocyanide-based MCRs for further scaffold differentiation. [56][57][58] A second MCR discovery approach that uses modular reaction sequences was reported by Zhu and co-workers.…”

Section: Modular Reaction Sequencesmentioning

confidence: 99%

Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

2011

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Multicomponent reactions have become increasingly popular as tools for the rapid generation of small-molecule libraries. However, to ensure sufficient molecular diversity and complexity, there is a continuous need for novel reactions. Although serendipity has always played an important role in the discovery of novel (multicomponent) reactions, rational design strategies have become much more important over the past decade. In this Review, we present an overview of general strategies that allow the design of novel multicomponent reactions. The challenges and opportunities for the future will be discussed.

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Section: Modular Reaction Sequencesmentioning

confidence: 99%

Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

2011

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“…Interessanterweise führt der Gebrauch von Isothiocyanaten als vierte Komponente zur Bildung von 2‐Aminothiazinen 65 , deren Dimroth‐Umlagerung unter Mikrowellenbestrahlung die Dihydropyrimidine‐2‐thione 66 ergibt 53. Die vielleicht faszinierendste Reaktion in dieser Gruppe ist die Umsetzung von Azadien 54 mit α‐Isocyanestern zu Isocyan‐substituierten Dihydropyridonen 67 54. 55 Die Isocyanidfunktion der Produkte ermöglicht die Kombination mit Isocyanid‐MCRs zur weiteren Gerüstdifferenzierung 56–58…”

Section: Rationale Entwicklung Von Mcrsunclassified

Charge‐Shift Bonding—A Class of Electron‐Pair Bonds That Emerges from Valence Bond Theory and Is Supported by the Electron Localization Function Approach

Shaik

Silvi

Lauvergnat

et al. 2005

Chemistry A European J

248

318

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This paper deals with a central paradigm of chemistry, the electron-pair bond. Valence bond (VB) theory and electron-localization function (ELF) calculations of 21 single bonds demonstrate that along the two classical bond families of covalent and ionic bonds, there exists a class of charge-shift bonds (CS bonds) in which the fluctuation of the electron pair density plays a dominant role. In VB theory, CS bonding manifests by way of a large covalent-ionic resonance energy, RE(CS), and in ELF by a depleted basin population with large variances (fluctuations). CS bonding is shown to be a fundamental mechanism that is necessary to satisfy the equilibrium condition, namely the virial ratio of the kinetic and potential energy contributions to the bond energy. The paper defines the atomic propensity and territory for CS bonding: Atoms (fragments) that are prone to CS bonding are compact electronegative and/or lone-pair-rich species. As such, the territory of CS bonding transcends considerations of static charge distribution, and involves: a) homopolar bonds of heteroatoms with zero static ionicity, b) heteropolar sigma and pi bonds of the electronegative and/or electron-pair-rich elements among themselves and to other atoms (e.g., the higher metalloids, Si, Ge, Sn, etc), c) all hypercoordinate molecules. Several experimental manifestations of charge-shift bonding are discussed, such as depleted bonding density, the rarity of ionic chemistry of silicon in condensed phases, and the high barriers of halogen-transfer reactions as compared to hydrogen-transfers.

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“…The test set contained the following compounds, synthesized in house and provided by the Section of Synthetic and Bio-organic Chemistry: BG168 [13], NEL3282A [14], NEL216BC [15], NEL269A [15], NEL235C [15], NEL285 [15], BG164 [16], DHP [17], NEL296A [15], NEL216 [15], NEL362B[14], NEL350 [14], MM-III-16-2C [18], VUA036 [19], VUA028 [19], MP84 [17], MP186 [20], MP161 [21]. The structures, molecular weights and some relevant physico-chemical properties of the compounds are given in Fig.…”

Section: Methodsmentioning

confidence: 99%

Direct Dynamic Protein-Affinity Selection Mass-Spectrometry

Jonker¹,

Lingeman²,

Irth³

2010

Chroma

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A new methodology is described enabling the affinity screening of potential ligands towards the human estrogen receptor alpha ligand binding domain (ERα-LBD). In-solution incubation is performed of the analyte and the His-tagged ERα-LBD. The bound complex is immobilized on a nickel-loaded protein-affinity selection column, where after the unbound fraction is removed. The immobilized protein–ligand complex is exposed to a decreased pH value and an increased organic modifier concentration releasing the ligand for MS detection, and precipitating the proteins on a filter positioned between the affinity column and the mass spectrometer. The trapping column can be regenerated for reuse at least 70 times. The advantages of the methodology over existing methodologies are the absence of a pre-concentration as well as a chromatographic separation step, resulting in a significantly shorter analysis time compared to previously described procedures, and in addition, allowing the determination of solutes with unfavorable chromatographic properties. The overall analysis time now can be reduced about 250% to approximately 6 min. Replacing the filters after every measurement results in an intra-day standard deviation of 14.8% and an inter-day standard deviation of 21.3%.

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Diastereoselective Multicomponent Synthesis of Dihydropyridones with an Isocyanide Functionality

Cited by 49 publications

References 26 publications

Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

Charge‐Shift Bonding—A Class of Electron‐Pair Bonds That Emerges from Valence Bond Theory and Is Supported by the Electron Localization Function Approach

Direct Dynamic Protein-Affinity Selection Mass-Spectrometry

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