Galactose catalytic oxidation

This compound is easily available by the pyrolysis of D-galactose [25] or, on the small scale, by Angyal and Beveridge s method [26]. Regioselective catalytic oxidation led to the corresponding 5-ulose which, via the oxime and subsequent reduction, could be converted into inhibitor (5) in approximately 6% overall... 

The isolation of D-fucose (6-deoxy-D-galactose) instead of galactose as a major product of the catalytic oxidation-reduction was considered to be the consequence of / -elimination of the initially formed 4-ulose-derivative. The removal of water resulted in the formation of a 4-keto-5,6-glucoseen which upon catalytic reduction yielded 6-deoxy-D-glactose. Thus, it seems that it is the intrinsic property of methyl-D-xylo-4-hexu-loside to undergo molecular rearrangement spontaneously. 

Copper would seem to be an appropriate choice of metal for the catalytic oxidation of alcohols with dioxygen since it comprises the catalytic centre in a variety of enzymes, e.g. galactose oxidase, which catalyze this conversion in vivo [188, 189]. Several catalytically active biomimetic models for these enzymes have been designed which are seminal examples in this area [190-193]. A complete overview of this field can be found in a review [194]. 

In 1998, a third efficient functional model of galactose oxidase was published by Saint-Aman et aL 86) who performed the electrochemical catalytic oxidation of primary alcohols to the corresponding aldehydes. was obtained from one equivalent Cu C104, 2 equivalents of triethylamine, and one equivalent of the ligand N,N-his (2-hydroxy-3,5-di- cr -butylbenzyl)-... 

The catalytic oxidation of the carbohydrates in the presence of Cu(II) for the detection of sucrose, galactose, and fructose was exploited using a Teflon-coated platinum wire plated with copper as the working electrode. Therefore, the addition of copper ions in the run buffer increased the sensitivity to an order of magnitude compared to run buffer without copper. Detection limits were 1 pmol 1 ... 

The realization of the widespread occurrence of amino acid radicals in enzyme catalysis is recent and has been documented in several reviews (52-61). Among the catalytically essential redox-active amino acids glycyl [e.g., anaerobic class III ribonucleotide reductase (62) and pyruvate formate lyase (63-65)], tryptophanyl [e.g., cytochrome peroxidase (66-68)], cysteinyl [class I and II ribonucleotide reductase (60)], tyrosyl [e.g., class I ribonucleotide reductase (69-71), photosystem II (72, 73), prostaglandin H synthase (74-78)], and modified tyrosyl [e.g., cytochrome c oxidase (79, 80), galactose oxidase (81), glyoxal oxidase (82)] are the most prevalent. The redox potentials of these protein residues are well within the realm of those achievable by biological oxidants. These redox enzymes have emerged as a distinct class of proteins of considerable interest and research activity. 

Bierenstiel and Schlaf [22] were able to prepare and isolate for the first time the less stable 8-D-galactonolactone by oxidation of galactose with the Schvo s catalytic system, which is based on the dimeric ruthenium complex [(C4Pli4CO)(CO)2Ru]2. The transformation led to the 5-galactonolactone in 93% yield, against 7% of the isolated y-lactone isomer. This procedure also allowed the preparation of 5-D-man-nonolactone in a much better yield (94%) than that reported in an early procedure [23] based on crystallization from a solution of calcium mannonate in aqueous oxahc acid. 

These systems are also described as normal copper proteins due to their conventional ESR features. In the oxidized state, their color is light blue (almost undetectable) due to weak d-d transitions of the single Cu ion. The coordination sphere around Cu, which has either square planar or distorted tetrahedral geometry, contains four ligands with N and/or 0 donor atoms [ 12, 22]. Representative examples of proteins with this active site structure (see Fig. 1) and their respective catalytic function include galactose oxidase (1) (oxidation of primary alcohols) [23,24], phenylalanine hydroxylase (hydroxy-lation of aromatic substrates) [25,26], dopamine- 6-hydroxylase (C-Hbond activation of benzylic substrates) [27] and CuZn superoxide dismutase (disproportionation of 02 superoxide anion) [28,29]. 

In contrast to the active site of galactose oxidase, to pre-catalyst 13, and to the system reported by Stack et al., the proposed catalytic species 15 does not imdergo reduction to Cu intermediates, as the oxidation equivalents needed for the catalysis are provided for solely by the phenoxyl radical Hgands. Since the conversion of alcohols into aldehydes is a two-electron oxidation process, only a dinuclear Cu species with two phenoxyl ligands is thought to be active. Furthermore, concentrated H2O2 is formed as byproduct in the reaction instead of H2O, as in the system described by Marko et al. [159]. 

Nonblue. These include galactose oxidase (GO) and amine oxidases (e.g., plasma amine oxidase, diamine oxidase, lysyl oxidase), which produce dihydrogen peroxide by the two-electron reduction of 02 [33], For GO (stereospecific primary alcohol oxidation), spectroscopic studies by Whittaker [70,71] suggest that the two-electron oxidation carried out by a mononuclear copper center is aided by a stabilized ligand-protein radical (i.e., (L)Cu(I) + 02 —> (L +)Cu(lI) + H202), obviating the need to get to Cu(III) in the catalytic cycle. Protein x-ray structures [33,72] reveal a novel copper protein cofactor, which would seem... 

An example of a one-pot, three-step catalytic cascade is shown in Fig. 1.51 [139]. In the first step galactose oxidase catalyses the selective oxidation of the primary alcohol group of galactose to the corresponding aldehyde. This is fol-... 

Fig. 21. Proposed catalytic mechanism for substrate oxidation by galactose oxidase. (A) Substrate binding displaces Tyr-495 phenolate which serves as a general base for abstracting the hydroxylic proton. (B) Stererospecihc pro- hydrogen abstraction by the Tyr-Cys phenoxyl radical. (C) Inner sphere electron transfer reducing Cu(II) to Cu(I). (D) Dissociation of the aldehyde product.

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