Ligand-Enabled Selective Coupling of MIDA Boronates to Dehydroalanine-Containing Peptides and Proteins

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7533 - 7544

Published: Feb. 21, 2025

α,β-dehydroalanine (ΔAla) is a uniquely reactive nonproteinogenic amino acid often employed for the late-stage functionalization of peptides, natural products (NPs), and proteins. The modification ΔAla powerful method semisynthetic engineering NPs post-translational protein mutagenesis. Numerous enabling techniques have been developed over years, but most state-of-the-art approaches furnish product mixtures detrimental in many applications. Here, we report Pd(II)-mediated coupling reaction between aryl N-methylimidodiacetic boronates ΔAla-containing peptides proteins which yields ΔzPhe with high selectivity. proceeds water under ambient conditions (37 °C, <24 h) without exclusion oxygen using fully unprotected substrates. speed selectivity enabled by use N,N'-ethylene-bis-Lthreonine as Pd(II) ligand. We utilize this chemistry to selectively functionalize variety oligopeptides, NP-like compounds, intact Finally, show that can be readily adapted modify vitro translated devising platform chemoribosomal synthesis ΔzPhe-containing structures. Altogether, our provides tool selective

Language: Английский

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Visible-Light-Mediated Solvent-Switched Photosensitizer-Free Synthesis of Polyfunctionalized Quinolines and Pyridines

Organic Letters, Journal Year: 2023, Volume and Issue: 25(3), P. 471 - 476

Published: Jan. 13, 2023

A solvent (2,2,2-trifluoroethanol (TFE) vs ethyl alcohol (EtOH)) switched synthesis of quinolines and pyridines is illustrated from (E)-2-(1,3-diphenylallylidene)malononitriles via a Pd(II)-catalyzed photochemical process. The active catalyst [L2Pd(0)] generated serves as an exogenous photosensitizer. process offers predominantly Z-alkenylated in TFE EtOH, respectively. Furthermore, large-scale few interesting post-synthetic modifications have been demonstrated.

Language: Английский

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Chalcogen Bonding in the Decoration of the Secondary Coordination Sphere of Copper(II) Complexes: Activation of Nitriles, the Auxiliary Ligand Substituent Effect

Crystal Growth & Design, Journal Year: 2023, Volume and Issue: 23(10), P. 7335 - 7344

Published: Aug. 30, 2023

The design of the secondary coordination sphere metal complexes has emerged as a powerful synthetic strategy in their application/function catalysis, molecular recognition, and crystal engineering. In contrast to traditional approaches, herein, copper(II) was designed by using chalcogen (sulfur) bond donor auxiliary ligands (5-substituted-1,3,4-thiadiazol-2-amines) one-pot activation one nitrile group an arylhydrazone ligand. ability markedly increases with electron-withdrawing character substituents, disclosed X-ray diffraction theoretical studies.

Language: Английский

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Regioselective Access to 1,2,4-Triazole-Fused N-Heterocycle, Pyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, via Double Dehydrative Cyclizations

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(16), P. 11748 - 11761

Published: Aug. 1, 2023

A highly efficient and regioselective approach to a novel 1,2,4-triazole-fused N-heterocyclic scaffold, pyrrolo[1,2-a][1,2,4]triazolo[3,4-c]pyrazine, was established by base-promoted reaction of pyrrole-2-carbonitrile-derived substrate with acyl hydrazide where domino double ring closures comprised enamine formation, attack on nitrile, cyclodehydration enabled sequential construction pyrazine 1,2,4-triazole systems formation three C-N bonds.

Language: Английский

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Palladium‐catalyzed Synthesis of Fused Carbo‐ and Heterocycles

Chemistry - An Asian Journal, Journal Year: 2022, Volume and Issue: 17(21)

Published: Sept. 6, 2022

The use of palladium catalysts in fused ring synthesis has been increasingly noteworthy recent years organic synthesis. It a lot potential compared to other transition metal catalysts, because its one-of-a-kind feature that makes them more widely applicable variety disciplines application. Palladium is important Heck processes, including intramolecular, intermolecular, and reductive reactions, which produce diverse carbocycles heterocycles biological importance. Under optimal reaction conditions, carbocyclization or heterocyclization occurs, resulting the production numerous structural building blocks naturally occurring compounds. Beside intramolecular Heck-type cycloaddition, cycloalkylation, oxidative coupling, C-H functionalization, cross-coupling carboamidation reactions have also employed extensively access carbo- immense This review article provides well-summarized discussion (since 2001) on heterocycle using overviewing their applications, mechanistic insights.

Language: Английский

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Mn‐Mediated Radical Cascade Cyclization of 1,6‐Enynes with Arylboronic Acids to Access Dihydrobenzo[b]fluorenones

Advanced Synthesis & Catalysis, Journal Year: 2022, Volume and Issue: 364(24), P. 4409 - 4414

Published: Dec. 1, 2022

Abstract Herein, we report the synthesis of functionalized dihydro‐benzo[ b ]fluorenones through a manganese‐mediated cascade radical cyclization β ‐alkynyl propenones [1,6‐enynes] with arylboronic acids. In present strategy, in‐situ generated aryl undergoes chemo‐selective addition followed by 5‐ exo‐trig cyclization. The reaction is emphasized high atom‐ and step‐economy construction three new C−C bonds to access dihydrobenzo[ in 68–81% yield under mild conditions. synthetic efficacy developed method evidenced C−N bonds. magnified image

Language: Английский

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Pd(II)-Catalyzed Three-Component Synthesis of Furo[2,3-d]pyrimidines from β-Ketodinitriles, Boronic Acids, and Aldehydes

Organic Letters, Journal Year: 2023, Volume and Issue: 25(50), P. 9070 - 9075

Published: Dec. 13, 2023

A Pd(II)-catalyzed three-component synthesis of 2,4,6-triarylfuro[2,3-d]pyrimidines from β-ketodinitriles, boronic acids, and aldehydes has been developed. The participation both nitrile (-CN) groups led to the concurrent construction furo-pyrimidine via formation C-C, C═C, C-O, C-N, C═N bonds. compounds show excellent photoluminescence properties with absorption maxima ranging 348 387 nm emission 468 533 nm. synthetic utility protocol was further demonstrated through a few postsynthetic manipulations.

Language: Английский

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Visible/solar-light-driven thiyl-radical-triggered synthesis of multi-substituted pyridines

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(8), P. 1680 - 1691

Published: Jan. 1, 2023

A light-triggered synthesis of thio-functionalized pyridines is demonstrated using γ-ketodinitriles, thiols, and eosin Y as the photocatalyst. The reaction proceeds via selective attack on one cyano groups by an in situ generated thiyl radical. also with nearly equal efficiency direct sunlight. Large-scale a few useful synthetic transformations substituted are performed.

Language: Английский

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Organic Base-Promoted C–N- and C–O-Coupled Domino Cyclization Strategy: Syntheses of Oxazine-6-ones and 4-Pyrimidinols

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(8), P. 5650 - 5664

Published: April 5, 2024

Oxazine-6-one and 4-pyrimidinol are two important frameworks in pharmaceutical production. Herein, we disclosed a simple, efficient, inexpensive organic base-promoted additive-stimulated protocol for the syntheses of variably functionalized oxazine-6-ones 4-pyrimidinols employing acetonitrile solvent under conventional heating conditions using an oil bath through C–N C–O coupled domino steps. This simple practicable productive utilizes easily producible cheap precursors, namely, benzimidates or benzamidines, with differently substituted dicyano-olefins, it comprises step economy, robustness, moisture insensitive affording high yield that avoids use transition-metal catalysts, multistep multicomponent strategy, harsh reaction involving hazardous chemicals. method is scalable into gram-scale production good yield.

Language: Английский

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Controlling (E/Z)‐Stereoselectivity of ‐NHC=O Chlorination: Mechanism Principles for Wide Scope Applications

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(60)

Published: July 3, 2024

Abstract Organic halogen compounds are cornerstones of applied chemical sciences. Halogen substitution is a smart molecular design strategy adopted to influence reactivity, membrane permeability and receptor interaction. Chiral bioreceptors may restrict the stereochemical requirements in halo‐ligand design. Straightforward (but expensive) catalyzed stereospecific halogenation has been reported. Historically, PCl 5 served access uncatalyzed stereoselective chlorination although outcomes were influenced by steric parameters. Nonetheless, investigation reaction mechanism with carbamoyl (RCONHX) never addressed. Herein, we provide first comprehensive mechanistic explanation outlining ; key regioselectivity‐limiting nitrilimine intermediate ( 8‐Z.HCl ); how pattern influences regioselectivity; why oxadiazole byproduct P1 ) encountered; stereo‐electronic factors influencing hydrazonoyl chloride P2 production; discovery two stereoselectivity‐limiting parallel mechanisms (stepwise concerted) elimination HCl POCl 3 . DFT calculations, synthetic methodology optimization, X‐ray evidence experimental kinetics study all supported suggested proposal (Scheme 2). Finally, mechanism‐inspired future recommendations for directing stereoselectivity toward elusive stereochemically inaccessible E ‐bis ‐hydrazonoyl chlorides along potentially pivotal applications both E/Z )‐stereoisomers especially medicinal chemistry protein modification.

Language: Английский

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