RESUMEN
We have identified an aminoacyl-tRNA synthetase/tRNA pair for the efficient and site-specific incorporation of a cyclobutene-containing amino acid into proteins in response to an amber nonsense codon. Fast and fluorescent labeling of purified proteins and intact proteins in live cells was demonstrated using the inverse electron demand Diels-Alder reaction with a tetrazine.
Asunto(s)
Aminoacil-ARNt Sintetasas/genética , Codón sin Sentido/genética , Ciclobutanos/química , Escherichia coli/citología , Colorantes Fluorescentes/química , ARN de Transferencia/genética , Aminoácidos/química , Aminoacil-ARNt Sintetasas/química , Aminoacil-ARNt Sintetasas/metabolismo , Supervivencia Celular , Reacción de Cicloadición , Ciclobutanos/síntesis química , Electrones , Colorantes Fluorescentes/síntesis química , Proteínas Fluorescentes Verdes/química , Modelos Moleculares , Estructura Molecular , ARN de Transferencia/química , ARN de Transferencia/metabolismo , Coloración y EtiquetadoRESUMEN
The Lewis acid-mediated reaction of alkene nucleophiles with peroxyacetals provides an effective route for the synthesis of homologated peroxides and hydroperoxides. In the presence of Lewis acids such as TiCl(4), SnCl(4), and trimethylsilyl triflate, peroxyacetals and peroxyketals undergo reaction with allyltrimethylsilane, silyl enol ethers, and silyl ketene acetals to afford homoallyl peroxides, 3-peroxyketones, and 3-peroxyalkanoates, respectively. Reactions of peroxyacetals are Lewis acid dependent; TiCl(4) promotes formation of ethers while SnCl(4) and trimethylsilyl triflate promote formation of peroxides. Lewis acid-promoted reactions of silylated hydroperoxyacetals furnish silylated hydroperoxides, which can be deprotected to homologated hydroperoxides. Hydroperoxyketals undergo Lewis acid-mediated allylation to furnish 1,2-dioxolanes via attack of hydroperoxide on the intermediate carbocation. Lewis acid-mediated cyclization of unsaturated peroxyacetals furnishes 1,2-dioxanes, 1,2-dioxepanes, and 1,2-dioxacanes through 6-endo/exo, 7-endo/endo, and 8-endo/endo pathways. The corresponding reactions involving 6-endo/endo and 5-endo/exo pathways were unsuccessful.
Asunto(s)
Carbono/química , Cationes Monovalentes/química , Peróxidos/síntesis química , Espectroscopía de Resonancia MagnéticaRESUMEN
The presence of Lewis acids strongly influences the distribution of products from alkene ozonolysis. Delivery of alkoxide and phenoxide ligands to a coordinated carbonyl oxide affords hydroperoxyacetals under aprotic conditions.
Asunto(s)
Ácidos/química , Óxidos/química , Ozono/química , EstereoisomerismoRESUMEN
A stable ozonide derived from Cbz-L-Phe accomplishes rapid and stoichiometric inhibition of papain at less than 100 microM concentration under conditions where formation of the corresponding aldehyde is negligible. Oxidation of the active site thiolate by the bound peroxide is believed to lead to formation of an inactive sulfenate or sulfenic acid. Reduction of the ozonide in excess DMSO provides a convenient method for in situ generation of a peptide aldehyde.
Asunto(s)
Aminoácidos/química , Inhibidores de Cisteína Proteinasa/farmacología , Ozono/química , Peróxidos/farmacología , Oxidación-ReducciónRESUMEN
[formula: see text] Addition of electron-rich alkenes to the peroxycarbenium ions derived from Lewis acid-mediated ionization of 3-alkoxy-1,2-dioxolanes provides an efficient route for the synthesis of substituted 1,2-dioxolanes. The methodology is illustrated with a rapid synthesis of a 1,2-dioxolane natural product related to the plakinic acids.
Asunto(s)
Ácidos/química , Dioxolanos/químicaRESUMEN
A general approach to E,E-diene hydroperoxides is described based upon photoisomerization of readily available Z,E-diene monoperoxyketals. Protection of a Z,E-diene hydroperoxide as the 2-methoxypropyl peroxyketal is followed by iodine-mediated photoisomerization to produce a mixture enriched in the E,E isomer. After chromatographic purification, deprotection of the peroxyketal with mild acid furnishes the E,E-diene hydroperoxide.