Elaboration of bromoarylnitriles

Parham, William E.; Jones, L.

doi:10.1021/jo00869a023

Cited by 71 publications

(40 citation statements)

References 4 publications

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“…4-Cyanobenzophenone (20) was prepared in two steps from 4-cyanobenzaldehyde and phenylmagnesium bromide by the procedure of Wagner and Siebert (21). HOPhHA was synthesized by a literature method (22).…”

Section: Methodsmentioning

confidence: 99%

Identification of a Firefly Luciferase Active Site Peptide Using a Benzophenone-based Photooxidation Reagent

Branchini

Magyar

Marcantonio

et al. 1997

Journal of Biological Chemistry

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Firefly luciferase catalyzes the highly efficient emission of yellow-green light from substrate luciferin by a series of reactions that require MgATP and molecular oxygen. We prepared 2-(4-benzoylphenyl)thiazole-4-carboxylic acid (BPTC), a novel benzophenone-based substrate analog, intending to use it in photoaffinity labeling studies to probe the luciferase active site. Instead, we found that while BPTC was a potent photoinactivating reagent for firefly luciferase, it was not a photoaffinity labeling agent. Using proteolysis, reverse phase high-performance liquid chromatography, tandem high performance liquid chromatography-electrospray ionization mass spectrometry, and Edman sequencing, we identified a single luciferase peptide, 244HHGF247, the degradation of which was directly correlated to luciferase photoinactivation. Results of enzyme kinetics and related studies were consistent with this peptide being at or near the luciferin binding site. Further, peptide model studies and additional investigations on the nature of the photoinactivation process strongly suggested that BPTC catalyzed the formation of singlet oxygen at the active site of the enzyme. We describe here an uncommon example of active site-directed photooxidation of an enzyme by singlet oxygen.Bioluminescence is a captivating process in which living organisms convert chemical energy into light. Beetle bioluminescence, including perhaps 2000 species of fireflies (1, 2), has provided a fertile area of basic and applied research mainly focused on the North American firefly Photinus pyralis. As Equations 1 and 2 indicate, the key firefly luciferase enzyme functions as a monooxygenase, although it does so without the apparent involvement of a metal or cofactor. By some means, amino acid residues are recruited to promote the addition of molecular oxygen to luciferin which is then transformed to an electronically excited state oxyluciferin molecule and CO 2 , each containing one oxygen atom from molecular oxygen. The light emission process is extremely efficient; nearly a single photon is emitted per reacted luciferin molecule (3).The luciferase-catalyzed reactions provide the basis for a wide variety of biochemical assays, many with important clinical applications (4, 5). Moreover, the luciferase gene (6) is widely used as a reporter in studies of gene expression and regulation (7). Additionally, the cloning and sequencing of P. pyralis luciferase and homologues from several beetles (8) have revealed that these enzymes are closely related to a large family of nonbioluminescent proteins (9, 10) that catalyze reactions of ATP with carboxylate substrates to form acyl adenylates.The recent solving of the crystal structure of luciferase without bound substrates or ligands revealed an apparently unique molecular architecture consisting of two distinct domains (11); however, a detailed description of the luciferase active site remains elusive. Early chemical modification studies have failed to document the involvement of any specific amino acid residues in s...

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Section: Methodsmentioning

confidence: 99%

Identification of a Firefly Luciferase Active Site Peptide Using a Benzophenone-based Photooxidation Reagent

Branchini

Magyar

Marcantonio

et al. 1997

Journal of Biological Chemistry

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“…(2'-Nitro-2'-propenyl)thiophene (18; Method B ) . A solution of 1.232 g (7.55 mmol) of 3-bromothiophene in 2 ml of THF was added dropwise to 7.6 mmol of BuLi in 5 ml of hexane THF I : 9 at -100" [32]. Stirring was continued for 0.25 h at -100".…”

Section: -(2'-nitro-2'-propenyl)-l-cyclohexanone (11 ; Methods A)mentioning

confidence: 99%

2′‐Nitro‐2′‐propen‐1′‐yl 2,2‐Dimethylpropanoate (NPP), A Multiple Coupling Reagent

Seebàch¹,

Konchel²

1984

Helvetica Chimica Acta

140

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SummaryThe title compound 1 (NPP) is prepared from formaldehyde, nitromethane, and pivaloyl chloride. It is shown to be a versatile nitroallylating reagent combining with nucleophiles as different as anilines, indoles, enolates, and organolithium compounds. This is documented by ca. 40 examples (2-30). The mechanism of the reaction is discussed. Some examples of addition of two different nucleophiles to the c,-moiety of NPP are described (35-46). This demonstrates the usefulness of NPP as a multiple coupling reagent for convergent syntheses, also of products not containing nitro groups (Scheme 4 ) .

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“…There are three general strategies in the literature for the synthesis of the exo-olefinic isoindolinone ring (Scheme 1): 1: enamine formation via hydroamine or condensation; 6-8 2: Heck type of intramolecular cyclization; 9-10 3: direct olefination of the lactam or imide precursors. [11][12][13][14] Despite these advances, the synthesis of 3-methyleneisoindolin-1-one analogues remain challenging for medicinal chemists due to the long synthetic efforts required to obtain appropriately substituted starting materials. More recently, a more straightforward C-H activation strategy was also developed.…”

Section: Introductionmentioning

confidence: 99%

A copper-catalyzed aerobic domino process for the synthesis of isoindolin-1-ylidene derivatives

2015

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Elaboration of bromoarylnitriles

Cited by 71 publications

References 4 publications

Identification of a Firefly Luciferase Active Site Peptide Using a Benzophenone-based Photooxidation Reagent

Identification of a Firefly Luciferase Active Site Peptide Using a Benzophenone-based Photooxidation Reagent

2′‐Nitro‐2′‐propen‐1′‐yl 2,2‐Dimethylpropanoate (NPP), A Multiple Coupling Reagent

A copper-catalyzed aerobic domino process for the synthesis of isoindolin-1-ylidene derivatives

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