Convenient procedure for the preparation of 2-arylazirines

Hortmann, Alfred G.; Robertson, Douglas D.; Gillard, Baiba K.

doi:10.1021/jo00967a033

Cited by 92 publications

(37 citation statements)

References 1 publication

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“…Synthesis of ␤,␤-Difluorophenethylamine Hydrochloride-Styrene was first converted to the azirine (2-phenyl-1-azirine) as described previously (33). To a solution of styrene (52.19 g, 57.5 ml, 0.50 mol) in 400 ml of CCl 4 in an ice bath was added a solution of bromine (80 g, 25.8 ml, 0.50 mol) in 100 ml of CCl 4 through an addition funnel over 30 min.…”

Section: Methodsmentioning

confidence: 99%

Evidence That Dioxygen and Substrate Activation Are Tightly Coupled in Dopamine β-Monooxygenase

Evans

Ahn

Klinman

2003

Journal of Biological Chemistry

181

268

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Oxygen activation occurs at a wide variety of enzyme active sites. Mechanisms previously proposed for the copper monooxygenase, dopamine ␤-monooxygenase (D␤M), involve the accumulation of an activated oxygen intermediate with the properties of a copper-peroxo or copper-oxo species before substrate activation. These are reminiscent of the mechanism of cytochrome P-450, where a heme iron stabilizes the activated O 2 species. Herein, we report two experimental probes of the activated oxygen species in D␤M. First, we have synthesized the substrate analog, ␤,␤-difluorophenethylamine, and examined its capacity to induce reoxidation of the prereduced copper sites of D␤M upon mixing with O 2 under rapid freeze-quench conditions. This experiment fails to give rise to an EPR-detectable copper species, in contrast to a substrate with a C-H active bond. This indicates either that the reoxidation of the enzyme-bound copper sites in the presence of O 2 is tightly linked to C-H activation or that a diamagnetic species Cu(II)-O 2 ⅐ ⅐ has been formed. In the context of the open and fully solvent-accessible active site for the homologous peptidylglycine-␣-hydroxylating monooxygenase and by analogy to cytochrome P-450, the accumulation of a reduced and activated oxygen species in D␤M before C-H cleavage would be expected to give some uncoupling of oxygen and substrate consumption. We have, therefore, examined the degree to which O 2 and substrate consumption are coupled in D␤M using both end point and initial rate experimental protocols. With substrates that differ by more than three orders of magnitude in rate, we fail to detect any uncoupling of O 2 uptake from product formation. We conclude that there is no accumulation of an activated form of O 2 before C-H abstraction in the D␤M and peptidylglycine-␣-hydroxylating monooxygenase class of copper monooxygenases, presenting a mechanism in which a diamagnetic Cu(II)-superoxo complex, formed initially at very low levels, abstracts a hydrogen atom from substrate to generate Cu(II)-hydroperoxo and substrate-free radical as intermediates. Subsequent participation of the second copper site per subunit completes the reaction cycle, generating hydroxylated product and water. Dopamine ␤-monooxygenase (D␤M) 1 along with peptidylglycine-␣-hydroxylating monooxygenase (PHM) comprise a unique class of enzymes that contain only copper as a cofactor and catalyze the cleavage of O 2 to form hydroxylated product and water. D␤M is of central importance in the catecholamine biosynthetic pathway, catalyzing the conversion of dopamine to norepinephrine (Scheme 1, top), where both substrate and product serve as neurotransmitters within the central nervous system (1). Primarily localized within the secretory granules of adrenal chromaffin cells and neurons, D␤M is a large, tetrameric glycoprotein (75 kDa per monomer) consisting of two disulfide-linked dimers.Although no crystal structure has been reported, extensive structural data exist for D␤M. Extended X-ray absorption fine structure was used to char...

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Section: Methodsmentioning

confidence: 99%

Evidence That Dioxygen and Substrate Activation Are Tightly Coupled in Dopamine β-Monooxygenase

Evans

Ahn

Klinman

2003

Journal of Biological Chemistry

181

268

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“…The azirines were prepared from the corresponding azidostyrenes. [8] Products given as traces were detected by GLC analyses.…”

Section: Methodsmentioning

confidence: 99%

New Cleavage of the Azirine Ring by Single Electron Transfer: The Synthesis of 2H-Imidazoles, Pyridazines and Pyrrolines

et al. 2001

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“…Subsequently, the method was adapted to be more amenable to the preparative scale, as exemplified by the synthesis of the trifluoromethylphenylazirine 184, which was carried out on a 10-gram scale [250]. The vinyl azide in this case was synthesized from the corresponding alkene (i.e., 182) through sequential bromination, azide displace- ment and dehydrobromination, a protocol used by Gilchrist and coworkers to access azirinyl esters [251,252].…”

Section: From Vinyl Azidesmentioning

confidence: 99%

Three‐Membered Heterocycles. Structure and Reactivity

Murphree

2011

Modern Heterocyclic Chemistry

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Convenient procedure for the preparation of 2-arylazirines

Cited by 92 publications

References 1 publication

Evidence That Dioxygen and Substrate Activation Are Tightly Coupled in Dopamine β-Monooxygenase

Evidence That Dioxygen and Substrate Activation Are Tightly Coupled in Dopamine β-Monooxygenase

New Cleavage of the Azirine Ring by Single Electron Transfer: The Synthesis of 2H-Imidazoles, Pyridazines and Pyrrolines

Three‐Membered Heterocycles. Structure and Reactivity

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