RESUMO
The Glaser-Hay coupling of terminal alkynes is a useful synthetic reaction for the preparation of polyynes; however, chemoselectivity issues have precluded its widespread utilization. Conducting the reaction on a solid-support provides a mechanism to alleviate the chemoselectivity issues and provide products in high purities and yields. Moreover, the polyyne core is a key component to several natural products. Herein, we describe the application of a solid-supported Glaser-Hay reaction in the preparation of several natural products. These compounds were then screened for antibacterial activity, illustrating the utility of the methodology.
Assuntos
Alcinos/química , Produtos Biológicos/síntese química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Catálise , Espectrometria de Massas , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
The site-specific incorporation of unnatural amino acids into proteins has a wide range of biological implications. Of particular interest is the incorporation of fluorescent probes as a mechanism to track protein function, transport, and folding. Thus, the development of a novel system for the incorporation of new fluorescent unnatural amino acids has significant utility. Specifically, we have elucidated an aminoacyl-tRNA synthetase capable of recognizing a terphenyl UAA derivative, and charging a cognate tRNA with this amino acid for protein incorporation. Moreover, we have successfully incorporated this fluorescent UAA into GFP at several key residues, demonstrating a novel means to modulate fluorescence within the protein.
Assuntos
Aminoacil-tRNA Sintetases/metabolismo , Compostos de Bifenilo/síntese química , Corantes Fluorescentes/síntese química , Proteínas de Fluorescência Verde/metabolismo , Fenilalanina/análogos & derivados , Compostos de Terfenil/síntese química , Substituição de Aminoácidos , Aminoacil-tRNA Sintetases/genética , Compostos de Bifenilo/metabolismo , Escherichia coli , Corantes Fluorescentes/metabolismo , Proteínas de Fluorescência Verde/genética , Mutagênese Sítio-Dirigida , Mutação , Fenilalanina/síntese química , Fenilalanina/metabolismo , Estrutura Terciária de Proteína , Compostos de Terfenil/metabolismoRESUMO
The prevalence of bioconjugates in the biomedical sciences necessitates the development of novel mechanisms to facilitate their preparation. Towards this end, the translation of the Glaser-Hay coupling to an aqueous environment is examined, and its potential as a bioorthogonal conjugation reaction is demonstrated. This optimized, novel, and aqueous Glaser-Hay reaction is applied towards the development of bioconjugates utilizing protein expressed with an alkynyl unnatural amino acid. Unnatural amino acid technology provides a degree of bioorthognality and specificity not feasible with other methods. Moreover, the scope of the reaction is demonstrated through protein-small molecule couplings, small-molecule-solid-support couplings, and protein-solid-support immobilizations.
Assuntos
Proteínas/química , Alcinos/química , Aminoácidos/química , Aminoacil-tRNA Sintetases/química , Aminoacil-tRNA Sintetases/metabolismo , Catálise , Cobre/química , Maleimidas/química , Compostos Organometálicos/química , Proteínas/metabolismo , Água/químicaRESUMO
The translation of organometallic reactions into a microwave reactor has numerous advantages. Herein, we describe the application of a previously developed solid-supported Glaser-Hay reaction to microwave conditions. Overall, an array of diynes has been prepared demonstrating the ability to conduct chemoselective reactions in the microwave within 20 min compared to the 16 h thermal conditions. Moreover, non-microwave transparent alkynes have been found to react more quickly, preventing catalyst quenching, and resulting in higher yields.
Assuntos
Di-Inos/síntese química , Catálise , Di-Inos/química , Micro-Ondas , Estrutura Molecular , Fatores de TempoRESUMO
Polyynes exhibit both unique photophysical properties and biological activities, necessitating efficient syntheses towards these core structures. A novel methodology for the construction of highly conjugated asymmetrical polyynes has been developed in a chemoselective fashion utilizing a solid-support. The synthesis has been applied to prepare a small library of polyynes in good to moderate yield. Moreover, their interesting fluorescence properties have been investigated, demonstrating the ability to tune fluorescence through selection of appropriate synthetic building blocks.
Assuntos
Poli-Inos/químicaRESUMO
While the Glaser-Hay coupling of terminal alkynes is a useful reaction, several issues associated with chemoselectivity preclude its widespread application in synthetic chemistry. To address these issues, a solid-supported Glaser-Hay methodology was developed to afford only asymmetric diyne products. This methodology was then applied to a series of immobilized alkynes with a diverse set of soluble alkynes to generate an array of heterocoupled products in high yields and purities.