Fremy's Salt Oxidation Research Articles

Mussel-inspired new approach for polymerization and cross-linking of peptides and proteins containing tyrosines by Fremy's salt oxidation.

Our objective was to develop a method mimicking the natural process of coherence in marine mollusks, by direct chemical conversion of protein tyrosine residues to DOPA-o-quinones, which consequently generates polymerization and cross-linking. Fremy's salt, (ON(SO3K)2, was used to convert tyrosine residues in peptides and proteins to reactive o-quinones. The conversion of tyrosines to DOPA-o-quinones, and their ability to polymerize or cross-link, was tested on tyramine, peptides, and proteins. The peptides tested were as follows: biotin-PEG4-tyramine (PEG-BT), and two decapeptides (identical to the repeating units comprising the mussel's adhesive protein). The proteins tested were as follows: bovine pancreatic ribonuclease A (RNase), lysozyme, IgG, avidin, and streptavidin. The oxidized peptides and proteins were all shown to incorporate oxygen atoms and undergo polymerization and cross-linking, depending on the availability of nucleophiles, mostly lysine amino groups of proteins. All the peptides and the noninteracting proteins such as RNase and lysozyme underwent homopolymerization upon Fremy's salt oxidation. When Fremy's salt oxidaized PEG-BT was mixed with the above proteins, it did not react with any of these proteins because PEG-BT underwent fast self-polymerization. Conversely, streptavidin or avidin cross-linked with PEG-BT after preincubation, thus showing that biorecognition is a prerequisite for cross-linking. Polymerization and cross-linking also occurred, following Fremy's salt oxidation of interacting proteins such as avidin and strepavidin with biotinyilated lysozyme or biotinylated RNase. This indicates that only proteins in very close proximity readily cross-link and polymerize via tyrosine residues. Attempts to convert DOPA-quinone to DOPA by reduction with sodium dithionite (Na2S2O4), was successful as far as small peptides were used. Fremy's salt oxidation can serve as an easy and useful tool to polymerize and cross-link proteins, for fabrication of biomaterials and to study protein-protein interactions.

Towards the Synthesis of Chiral Isochromanquinones. The Use of Corey—Bakshi—Shibata Reductions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Towards the synthesis of chiral isochromanquinones. The use of Corey–Bakshi–Shibata reductions

(1 R,3 R,4 S)-3,4-Dihydro-4-hydroxy-6-methoxy-1,3-dimethylisochroman-5,8-dione has been synthesized in 65% ee from (1 R,3 R,4 S)-5-benzyloxy-3,4-dihydro-4-hydroxy-6-methoxy-1,3-dimethylisochroman by catalytic hydrogenolysis followed by Fremy's salt oxidation of the derived phenol. The latter isochroman was synthesized from a mercury(II) mediated oxidative cyclization of ( R)-3-benzyloxy-4-methoxy-1-(1′-hydroxyethyl)-2-prop-1′-enylbenzene which in turn was obtained in 75% ee from the chiral reduction of 1-acetyl-3-benzyloxy-4-methoxy-2-prop-1′-enylbenzene with borane–methylsulfide complex in the presence of the Corey–Bakshi–Shibata catalyst.

Synthesis of ABC Analogues of the Antitumour Antibiotic Streptonigrin

ABC analogues of the antitumour antibiotic streptonigrin, that contain the key metal chelation site and redox-active quinone unit that are essential for biological activity, were prepared via palladium catalysed cross-coupling of 2-iodo-8-nitroquinoline or 2-iodo-6-methoxy-5-nitroquinoline with 2-trimethylstannio-6-methylpyridine. Mild oxidation of the pyridyl methyl group introduced the acid functional group on ring C and Fremy's salt oxidation afforded the quinone unit which was elaborated to give the 5-amino-6-methoxy substitution pattern present in streptonigrin.

Synthesis of azanzone A, a new naturally occurring o-naphthoquinone

The synthesis is reported of 7-hydroxy-5-isopropyl-3,8-dimethylnaphthalene-1,2-dione 2 which was found to be identical with the natural product azanzone A, thus confirming the structure of the latter. The synthesis was achieved using the Stobbe condensation to obtain the butanedioic acid mono-ester 8 which readily cyclised to give the naphthoate 9. Reduction of the ester to a methyl group, followed by Fremy's salt oxidation and O-demethylation with boron tribromide completed the synthesis.

On the regioselectivity of the fremy's salt oxidation of phenols

A detailed study of the regioselectivity of the Fremy's salt oxidation of phenols, including a series of MNDO calculations of the intermediate phenoxy radicals, has been carried out. The analysis of these results has led us to establish a new rule for the para vs. ortho regioselectivity, namely: “C-4 unsubstituted phenols, as well as phenols substituted at C-4 with easy-to-displace groups, undergo oxidation (or oxidative degradation) by the action of Fremy's salt, thus eventually providing the corresponding p-quinones”. A similar rule for the ortho vs. ortho' regioselectivity could not be so precisely formulated since now steric effects play a significant major role.

ChemInform Abstract: A Facile Synthesis of 1,4‐Benzoquinones Having a Hydroxyalkyl Side Chain.

AbstractZunächst werden entsprechend den Umsetzungen des Formelschemas auf verschiedenen Wegen die (o‐Acetoxyalkansäuren (III) dargestellt und in die Säurechloride (XII) übergeführt.

A facile synthesis of 1,4-benzoquinones having a hydroxyalkyl side chain.

6-(ω-Hydroxyalkyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinones (3) and 6-(ω-acetoxyalkyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinones (26) having various carbon numbers (n) of the side chain were synthesized by the Friedel-Crafts coupling of 3, 4, 5-trimethoxytoluene (4) and ω-acetoxyalkanoyl chlorides (5) as a key step. The Fremy's salt oxidation or the salcomine-catalyzed oxidation of 6-(ω-hydroxyalkyl)-2, 3-dimethoxy-5-methylphenols (25) and their acetates (24), the key intermediates of the process, gave rise to 3 and 26, respectively, in good yields. The described method provides a good yield of the 1, 4-benzoquinones and is suitable for the synthesis of other quinonyl analogs. The effect on lipid peroxidation in canine brain homogenate of the 1, 4-benzoquinones (3) having various carbon numbers (n) of the side chain was studied. Among the compounds tested, 3 having a carbon number in the range of n=9-13 showed rather strong antioxidant activity.

Fremy's salt oxidation of benzylamines. An oxidative deamination reaction

Fremy's salt is shown to oxidize efficiently primary benzylamines to imines, benzaldehydes and nitriles.

Synthesis of oxoaporphines. An unusual photocyclization-photoreduction of 2,3-diaryl-.DELTA.2-pyrroline-4,5-diones

The photocyclization of substituted 2,3-diaryl-Δ 2 -pyrroline-4,5-diones, with a forced cisstilbene geometry, afforded the corresponding phenanthrene derivatives. Concomitant photoreduction of the C-4 carbonyl group to methylene has been observed when triethylamine was used as acid scavenger. The role of the amine in the photocyclization and photoreduction steps is discussed in terms of the results obtained with different amines (triethylamine, pyridine, and tert-butylamine). The naturally occurring oxoglaucine, lysicamine, and dicentrinone have been synthesized in good to acceptable yields by Fremy's salt oxidation of the photocyclized products. © 1982, American Chemical Society. All rights reserved.

Fremy's salt oxidation of some isoquinoline alkaloids. Biogenetic considerations

Fremy's salt oxidation of benzyl isoquinoline and aporphine alkaloids to isoquinolones and oxoaporphines is described. Aminium radicals are suggested to account for the observed results. Their possible involvement in alkaloid biosynthesis is considered.

The neoflavanoid group of natural products—III: The synthesis and nuclear magnetic resonance spectra of the dalbergiones

The synthesis of the racemates (±_-4-methoxydalbergione (IIIa) and (±)-3,4-dimethoxydalbergione (IIIb) has been achieved by Claisen rearrangements of the corresponding cinnamyl ethers (Ia and Ib) followed by Fremy's salt oxidation. These syntheses are based upon the biosynthetic schemes examined in Part II of this series. The NMR spectra of the dalbergiones and their derivatives are discussed.