Photochemical transformations of small ring heterocyclic compounds. 9. Intramolecular 1,3-dipolar cycloaddition reactions of alkenyl-subituted nitrile imines

Padwa, Albert; Nahm, Steven; Sato, Eisuke F.

doi:10.1021/jo00403a009

Cited by 76 publications

(34 citation statements)

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“…[12] Despite its robust mechanism, this photoactivated reaction has seen very few applications in the past four decades. [13] In our initial studies, we identified an extremely mild photoactivation procedure in the use of a hand-held UV lamp from UVP (UVM-57, 302 nm, 115 V, 0.16 amps). Under these mild conditions, the solvent compatibility, functional-group tolerance, regioselectivity, and yield of the photoactivated 1,3-dipolar cycloaddition reaction were excellent.…”

mentioning

confidence: 99%

A Photoinducible 1,3‐Dipolar Cycloaddition Reaction for Rapid, Selective Modification of Tetrazole‐Containing Proteins

et al. 2008

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Bioorthogonal chemistry provides an exciting new strategy to visualize protein expression, track protein localization, measure protein activity, and identify protein interaction partners in living systems.[1] Two steps are typically involved in this approach: 1) the incorporation of a bioorthogonal group into a protein through either a biochemical pathway or semisynthesis; 2) a site-specific reaction between the protein that carries the bioorthogonal group and a cognate small-molecule probe. Although a plethora of methods have been developed to address the first step, such as non-sense suppression mutagenesis, [2] expressed protein ligation, [3] metabolic engineering, [4] and tagging-via-substrate, [5] only a small number of bioorthogonal reactions are known for the second step. These site-specific reactions include the acid-catalyzed nucleophilic addition of hydrazine to a ketone or aldehyde, [6] Staudinger ligation, [7] Cu I -catalyzed azide-alkyne 1,3-dipolar cycloaddition (click chemistry), [8] strain-promoted azide-alkyne 1,3-dipolar cycloaddition, [9] and the oxidative coupling of aniline.[10] To fully realize the potential of bioorthogonal chemistry in probing protein function, there is an urgent need for the discovery of additional bioorthogonal reactions with robust reaction attributes. Herein, we report a bioorthogonal, photoinducible 1,3-dipolar cycloaddition reaction that allows rapid and highly selective modification of proteins carrying a diaryl tetrazole group in biological media.Forty years ago, Huisgen and co-workers reported a photoactivated 1,3-dipolar cycloaddition reaction between 2,5-diphenyltetrazole and methyl crotonate.[11] A concerted reaction mechanism was proposed, whereby the diaryl tetrazole undergoes a facile cycloreversion reaction upon photoirradiation to release N 2 and generate in situ a nitrile imine dipole, which cyclizes spontaneously with an alkene dipolarophile to afford a pyrazoline cycloadduct (Scheme 1). The photolysis of diaryl tetrazoles was found to be extremely efficient upon UV irradiation at 290 nm, with quantum yields in the range 0.5-0.9.[12] Despite its robust mechanism, this photoactivated reaction has seen very few applications in the past four decades.[13]In our initial studies, we identified an extremely mild photoactivation procedure in the use of a hand-held UV lamp from UVP (UVM-57, 302 nm, 115 V, 0.16 amps). Under these mild conditions, the solvent compatibility, functional-group tolerance, regioselectivity, and yield of the photoactivated 1,3-dipolar cycloaddition reaction were excellent. [14] We then examined the reaction kinetics by incubating a tetrazole peptide with acrylamide in phosphate-buffered saline (PBS) at pH 7.5 under UV light (302 nm; see Figure S1 in the Supporting Information). We found that the photolysis of the tetrazole peptide to generate the nitrile imine intermediate was extremely rapid, with a first-order rate constant k 1 = 0.14 s À1 ; the subsequent cycloaddition with the dipolarophile acrylamide proceeded very efficiently, w...

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confidence: 99%

A Photoinducible 1,3‐Dipolar Cycloaddition Reaction for Rapid, Selective Modification of Tetrazole‐Containing Proteins

et al. 2008

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“…However, should a more active dipolarophile, such as dimethyl acetylenedicarboxylate, be present, bimolecular 1,3-dipolar cycloaddition results giving the monocyclic pyrazole 52 (Scheme 16). [47] Identical results are obtained when the intermediate nitrile imine is formed by dehydrochlorination of the appropriate hydrazonoyl chloride with a base.…”

Section: -Ethyl 3-methyl 1-(4-tolyl)-45-dihydro-1h-pyrazole-35-dicmentioning

confidence: 87%

“…Scheme 16 Nitrile Imine Generation from the Photolysis of Tetrazoles [47] Ph N N + Photolysis of 3,5-diphenyl-1,3,4-oxadiazol-2(3H)-one (53) generates benzonitrile anilide (34). This intermediate can be trapped with a variety of dipolarophiles including acrylonitrile, which gives the dihydropyrazole 54 in 96% yield (Scheme 17).…”

Section: -Ethyl 3-methyl 1-(4-tolyl)-45-dihydro-1h-pyrazole-35-dicmentioning

confidence: 99%

Product Class 2: Nitrile Imines

Murahashi¹

2004

Category 3, Compounds With Four and Three Carbon Heteroatom Bonds

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“…The cycloaddition is faster in water thanks to the hydrophobic effect [19]. Despite these favorable features, tetrazoles were used mostly in the synthesis of heterocyclic compounds [20, 21] and in polymer and material sciences [22] for a long time.…”

Section: Photoinduced 13-dipolar Cycloaddition Reaction Between Tementioning

confidence: 99%

Photo-Triggered Click Chemistry for Biological Applications

2015

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In the last decade and a half, numerous bioorthogonal reactions have been developed with a goal to study biological processes in their native environment, i.e., in living cells and animals. Among them, the photo-triggered reactions offer several unique advantages including operational simplicity with the use of light rather than toxic metal catalysts and ligands, and exceptional spatiotemporal control through the application of an appropriate light source with pre-selected wavelength, light intensity and exposure time. While the photoinduced reactions have been studied extensively in materials research, e.g., on macromolecular surface, the adaptation of these reactions for chemical biology applications is still in its infancy. In this chapter, we review the recent efforts in the discovery and optimization the photo-triggered bioorthogonal reactions, with a focus on those that have shown broad utility in biological systems. We discuss in each cases the chemical and mechanistic background, the kinetics of the reactions and the biological applicability together with the limiting factors.

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Photochemical transformations of small ring heterocyclic compounds. 9. Intramolecular 1,3-dipolar cycloaddition reactions of alkenyl-subituted nitrile imines

Cited by 76 publications

References 1 publication

A Photoinducible 1,3‐Dipolar Cycloaddition Reaction for Rapid, Selective Modification of Tetrazole‐Containing Proteins

A Photoinducible 1,3‐Dipolar Cycloaddition Reaction for Rapid, Selective Modification of Tetrazole‐Containing Proteins

Product Class 2: Nitrile Imines

Photo-Triggered Click Chemistry for Biological Applications

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