Easy does it: A wide range of N‐fused indole skeletons, which are core structures of many biologically potent molecules, are successfully furnished by a niobium‐catalyzed C(sp3)H insertion reaction (see picture). The precursors are readily prepared by a palladium‐catalyzed amination reaction of bromotrifluorotoluenes with cyclic amines.
So einfach ist das: Vielfältige N‐anellierte Indolgerüste, die als Kernstrukturen in zahlreichen biologisch aktiven Verbindungen auftreten, können mithilfe einer Niob‐katalysierten C(sp3)‐H‐Insertion aufgebaut werden (siehe Schema). Die Vorstufen sind leicht durch die Palladium‐katalysierte Aminierung von Bromtrifluortoluolen mit cyclischen Aminen zugänglich.
We developed an ovel diazirine-based photolabeling agent having a( coumarin-4-yl)methyl ester scaffold, which exhibited multiple photochemical properties of crosslinking, fluorogenicitya nd cleavage. These properties can be kinetically regulated via photoinduced electron transfer between diazirinea nd coumarin moieties. The CÀ Ob ond of (coumarin-4-yl)methyl ester can be cleaved via photochemical excitation of coumarin moiety,t hat function hasb een initially quenched by the diazirine moiety. Upon diazirine photolysis with 365-nm light, interacting protein was stably captured with photoactivatable ligand probe. Then, the unlocked cleavage functionw as activated with 313 nm light, and the reactionw as accelerated in aw eakly-basic solution.T he crosslinkedp rotein could be selectively isolated with attachment of as mall coumarin tag on the surface. This multi-functional labeling agent has ag reat potentialt of acilitateL C-MS/MS-based protein identification.Identification of proteinsi nteracting bioactive moleculesi sa fundamental research topic in the fields of life sciences and drug discovery.C hemical and photochemical covalent crosslinking of noncovalent biomolecular interactions allows the captureo fw eak and transient ligand-protein interactions and identification of agglutinate or degradable proteins. [1] The excellent photoreactivity of diazirine (DA), ac arbene precursor, has been applied for in situ photoaffinity labeling (PAL) and has contributed to the profiling of interacting proteins. [2] Upon UV irradiation, DA instantaneously forms as table covalent bond between spatially adjacent molecules. However,t he quantity of the labeled target protein is generally very small; therefore, the labeled protein needs to be enriched by applying efficient purification methodologies using biotin/avidin, [3] perfluoroalkane/fluorouss ilica, [4] immunoprecipitation using antibodies against bait proteins to detect protein-protein interaction, or post-labelingi nc ombination with other chemical reporterss uch as click tags [5] before mass spectrometry (MS)based identification.T he target can be shortlisted from many candidates by comparative analysisi nv arious conditions. Through diminishing false identification [6] due to nonspecific adsorbed proteins and some residual contaminants on the support, the combination of PALw ith quantitative proteomic techniques such as stable isotope labeling by amino acids in cell culture (SILAC), [7] intensity-based absolute quantification (iBAQ), [8] isobaric tags for relative and absolute quantification (iTRAQ) [9] enables quantitative profiling of modification sites. Alternatively,m ulti-functional crosslinkers having severalh ighsensitivef unctions such as scissile, fluorescencea nd stable isotope showed excellent performanceo nf ocusing the labeled peptides tep-by-step with different property during processes of protein enrichmenta nd liquid chromatography (LC)-MS/MS analysis. [10] Identification based on sequencing of the labeled peptide should be more direct and reliabl...
N‐Fused indoles appear in the structures of various biologically active molecules, but synthesis of the fused‐ring substructure has proved difficult. T. Akiyama and co‐workers describe in their Communication on a new route in which a niobium carbenoid is generated by niobium‐catalyzed activation of the normally inactive C–F bonds of a CF3 group. The carbenoid then undergoes insertion into a neighboring C(sp3)H bond adjacent to a nitrogen atom to furnish the N‐fused indole skeleton.
N‐anelliertes Indol findet sich in den Strukturen verschiedener biologisch aktiver Moleküle, allerdings hat sich die Synthese der entsprechenden Teilstruktur als schwierig erwiesen. T. Akiyama et al. beschreiben in der Zuschrift auf eine neue Syntheseroute, in der durch Aktivierung der normalerweise inaktiven C‐F‐Bindungen einer CF3‐Gruppe mit einem Niobkatalysator ein Niob‐Carbenoid gebildet wird. Dieses inseriert in eine benachbarte C(sp3)‐H‐Bindung neben einem N‐Atom unter Bildung des N‐anellierten Indols
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