Flavin catalysts

Baeyer-Villiger oxidation of ketones, in the presence of flavin catalyst, resulted in an excellent yield of the ester. A new flavin-type catalyst, 5-ethyl-3-methyl-2,4, 3/,5,-di-O-methyleneriboflavinium perchlorate, have been synthesized and used in these reactions.221... 

Scheme 11.3 A flavin-catalyst for the aerobic generation of diimide from hydrazine.

Thioethers can be oxidized to sulfoxides by 1 equivalent of 30% H2O2 or by many other oxidizing agents, including H202-flavin catalyst, H2O2 and a... 

More recently, a modification of the structure of these flavins gave more efficient and robust organocatalysts for the H202-based sulfoxidations [46]. These new flavin catalysts (19) are superior to the previous natural-based flavin catalysts and have the advantage that they also give excellent results for the oxidation of tertiary amines to amine oxides [47] (see Section 8.3.2). 

H2O2 oxidation of various sulfides to sulfoxides. The sulfoxides were obtained in good to high yields and high selectivity without any detectable overoxidation to sulfone. More importantly, the flavin catalyst 26 in the ionic liquid was recycled up to seven times in the sulfoxidation of some representative sulfides without loss of activity or selectivity (Table 8.6) [50]. According to NMR, the zwitterionic form of flavin 26 predominates, which explains why 26 stays in the ionic liquid after the extraction of the product. 

Table 8.6 Recycling of the flavin-catalyst in ionic liquid.

TABLE 6.5 Synthesis of Optically Active Sulfoxides Employing Novel Oxidative Flavin Catalysts Linked to RfBP... 

SCHEME 32.7. Diimide double-bond reduction using flavin catalyst ... 

It was shown subsequently that using an oxygen atmosphere and their flavin catalyst 7, even highly sensitive compounds could be reduced without racemization or other unwanted side effects (Scheme 32.10). 

Oxidation of P-nicotinamide adenine dinucleotide (NADH) to NAD+ has attracted much interest from the viewpoint of its role in biosensors reactions. It has been reported that several quinone derivatives and polymerized redox dyes, such as phenoxazine and phenothiazine derivatives, possess catalytic activities for the oxidation of NADH and have been used for dehydrogenase biosensors development [1, 2]. Flavins (contain in chemical structure isoalloxazine ring) are the prosthetic groups responsible for NAD+/NADH conversion in the active sites of some dehydrogenase enzymes. Upon the electropolymerization of flavin derivatives, the effective catalysts of NAD+/NADH regeneration, which mimic the NADH-dehydrogenase activity, would be synthesized [3]. 

A still more complicated reaction is the chemiluminescent oxidation of sodium hydrogen sulfide, cysteine, and gluthathione by oxygen in the presence of heavy metal catalysts, especially copper ions 60>. When copper is used in the form of the tetrammin complex Cu(NH3) +, the chemiluminescence is due to excited-singlet oxygen when the catalyst is copper flavin mononucleotide (Cu—FMN), additional emission occurs from excited flavin mononucleotide. From absorption spectroscopic measurements J. Stauff and F. Nimmerfall60> concluded that the first reaction step consists in the addition of oxygen to the copper complex ... 

The straightforward concept for the direct light-driven regeneration of flavin-dependent enzymes has been successfully applied for two representative classes of such enzymes a reductase and a monooxygenase. Therefore, it can be expected that this concept can also be applied to other flavin-dependent enzymes, potentially leading to additional practical catalyst systems for applications in synthetic organic chemistry. 

These flavopapains (Fig. 19) were shown to be effective redox catalysts for the oxidation of hT-alkyl-l,4-dihydronicotinamides. The localization of the flavin moiety adjacent to the hydrophobic binding groove of the active site further allowed the constructs to exhibit substrate selectivity and, in some cases, saturation kinetics. The most effective flavopapain was the 8-isomer (FP-8) which reacted rapidly with a variety of M-alkyl-1,4-dihydronicotinamides. The best substrate was N-hexyl-l,4-dihydronicotinamide for which the of its... 

In addition to the catalysts listed in Table 2, several rhodium(I) complexes of the various diphosphines prepared by acylation of bis(2-diphenylphosphinoethyl)amine were used for the hydrogenation of unsaturated acids as well as for that of pyruvic acid, aUyl alcohol and flavin mononucleotide [59,60]. Reactions were mn in 0.1 M phosphate buffer (pH = 7.0) at 25 °C under 2.5 bar H2 pressure. Initial rates were in the range of 1.6-200 mol H2/molRh.h. 

Bis-hydroxylation. Molecular oxygen or air was used as the terminal oxidant in the osmium-catalyzed oxidation of alkenes to form cis-diols with high conversions at low catalyst amount.1298 In a triple catalytic system using H2O2 as the terminal oxidant, a cinchona alkaloid ligand has a dual function—it provides stereocontrol and acts as reoxidant via its IV-oxide. The formation of the latter is catalyzed by a biomimetic flavin component.1299... 

In most organisms undergoing aerobic metabolism, pyruvate is oxidized to acetyl-CoA in a complex process involving its decarboxylation (Eq. 10-6). This oxidative decarboxylation, like the decarboxylation of pyruvate to acetaldehyde, requires thiamin diphosphate. In addition, an array of other catalysts participate in the process (see Fig. 15-15). Among these are the electron carrier flavin adenine diphosphate (FAD), which is derived from the vitamin riboflavin. Like NAD+, this... 

Warburg and Christian showed that the color of this old yellow enzyme came from a flavin and proposed that its cyclic reduction and reoxidation played a role in cellular oxidation. When NADP+ was isolated the proposal was extended to encompass a respiratory chain. The two hydrogen carriers NADP+ and flavin would work in sequence to link dehydrogenation of glucose to the iron-containing catalyst that interacted with oxygen. While we still do not know the physiological function of the old yellow enzyme,b the concept of respiratory chain was correct. 

This unique redox catalyst links the oxidation of H2 or of formate to the reduction of NADP+229 and also serves as the reductant in the final step of methane biosynthesis (see Section E) 228 It resembles NAD+ in having a redox potential of about -0.345 volts and the tendency to be only a two-electron donor. More recently free 8-hydroxy-7,8-didemethyl-5-deazaribo-flavin has been identified as an essential light-absorbing chromophore in DNA photolyase of Methanobacterium, other bacteria, and eukaryotic algae.230 Roseoflavin is not a coenzyme but an antibiotic from Streptomyces davawensisP1 Many synthetic flavins have been used in studies of mechanisms and for NMR232 and other forms of spectroscopy. 

Metalloenzymes or metal ion-activated enzymes catalyze an enormous variety of organic reactions that are not restricted to any particular reaction class, but appear as catalysts for all types of reactions. Thus neither the presence of the metal ion nor the reaction type seems to be restrictive as far as metal-assisted enzyme catalysis is concerned. In some cases the metal ion appears to function as an electron acceptor or donor, but flavin cofactors have substituted as redox centers during evolution in some enzymes. 

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