Glyoxylate hydrates

Scheme 56 Arylation of glyoxylate hydrates with Ar3Bi...

When the rhodium-catalyzed reaction of aryllead reagents in water and under an atmosphere of air was applied to a chiral glyoxylate hydrate, it gave the corresponding addition products in high yields (Equation (116)). The diastereoselectivity of the reactions were remarkably improved by using water as the solvent.128... 

After one month, a high degradation rate is observed and ethyl glyoxylate hydrate (EtGH), which is usually hydrolyzed into GAH, may be detected. 

Acetoxyalkoxyacetic esters 1 are readily prepared in two steps (eq 1) from methyl glyoxylate hydrate and the unsaturated alcohol ROH. Under the influence of tin tetrachloride in dichloromethane, esters 1 are converted into the very electrophilic methoxycarbonyloxonium intermediates 2. 

Reductive alkylation has been used to prepare a-amino acids suitable for lactam formation and further elaboration. In a single step a carbobenzyloxy group was removed, and alkylation with glyoxylic acid hydrate was achieved (18). 

Lubineau and coworkers [18] have shown that glyoxal 8 (Ri = R2 = H), glyoxylic acid 8 (Ri = H, R2 = OH), pyruvic acid 8 (Ri = Me, R2 = OH) and pyruvaldehyde 8 (Ri = H, R2 = Me) give Diels-Alder reactions in water with poor reactive dienes, although these dienophiles are, for the most part, in the hydrated form. Scheme 6.6 illustrates the reactions with (E)-1,3-dimethyl-butadiene. The reaction yields are generally good and the ratio of adducts 9 and 10 reflects the thermodynamic control of the reaction. In organic solvent, the reaction is kinetically controlled and the diastereoselectivity is reversed. 

Si. rra(pentafluorophenyl)boron was found to be an efficient, air-stable, and water-tolerant Lewis-acid catalyst for the allylation reaction of allylsilanes with aldehydes.167 Sc(OTf)3-catalyzed allylations of hydrates of a-keto aldehydes, glyoxylates and activated aromatic aldehydes with allyltrimethylsilane in H2O-CH3CN were examined. a-Keto and a-ester homoallylic alcohols and aromatic homoallylic alcohols were obtained in good to excellent yields.168 Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex (Eq. 8.71).169... 

Montmorillonite K10 was also used for aldol the reaction in water.280 Hydrates of aldehydes such as glyoxylic acid can be used directly. Thermal treatment of K10 increased the catalytic activity. The catalytic activity is attributed to the structural features of K10 and its inherent Bronsted acidity. The aldol reactions of more reactive ketene silyl acetals with reactive aldehydes proceed smoothly in water to afford the corresponding aldol products in good yields (Eq. 8.104).281... 

Aliphatic carboxylic acids are difficult to reduce electroehemically. Reduction of a 10% oxalic acid in 10% H2SO4. at 15 °C at a mercury cathode (Refs. [494, 532] in Ref. [29]), a lead or amalgamated lead cathode (Ref. [495] in Ref. [29]) or at a sodium amalgam (Na(Hg) cathode (Ref. [497] in Ref. [29]) produces glyoxylic acid with a material yield of 88% and a current efficiency of 70%. The glyoxylic acid formed is stabilized by hydration [29]. 

Fig. 9. Pathway duplication the methyl citrate cycle and the glyoxylate shunt. A pathway for acetate metabolism in E. coli that uses the glyoxylate shunt is depicted on the right. Part of the methyl citrate cycle, a pathway for propionate metabolism, is depicted on the left. The pathways are analogous furthermore, three of the four steps are catalyzed by homologous enzymes. PrpE (propionyl-CoA synthase) is homologous to AcsA (acetyl-CoA synthase). PrpC (2-methyl-citrate synthase) is homologous to GltA (citrate synthase). PrpB (2-methyl-isocitrate lyase) is homologous to AceA (isocitrate lyase). The third step in the methyl citrate cycle has been suggested to be catalyzed by PrpD the second half of the reaction (the hydration) can be catalyzed by aconitase.

Cleavage of the oxirane C-0 bond produces a zwitterionic intermediate (Fig. 10.22), which that can undergo chloride shift (Pathway a) to 2,2-dich-loroacetyl chloride (10.90) followed by hydrolysis to 2,2-dichloroacetic acid (10.91). Furthermore, the zwitterionic intermediate reacts with H20 or H30+ (Pathway b) by pH-independent or a H30+-dependent hydrolysis, respectively. The pH-independent pathway only is shown in Fig. 10.22, Pathway b, but the mechanism of the H30+-dependent hydrolysis is comparable. Hydration and loss of Cl, thus, leads to glyoxylyl chloride (10.92), a reactive acyl chloride that is detoxified by H20 to glyoxylic acid (10.93), breaks down to formic acid and carbon monoxide, or reacts with lysine residues to form adducts with proteins and cytochrome P450 [157], There is also evidence for reaction with phosphatidylethanolamine in the membrane. 

Further selectivity is needed if the enol component is an unsymmetrical ketone. Some selectivity can be achieved by choice of acid, favouring the more substituted enol, or base, favouring kinetic enolate formation on the less substituted side. The acid 32 was used at a very early stage of Woodward and Eschenmoser s synthesis5 of vitamin Bi2. Standard a -unsaturated carbonyl disconnection revealed unsymmetrical ketone 33 and unenolisable but very electrophilic glyoxylic acid 34 available as its hydrate. In acid solution reaction occurred very selectively indeed. 

Glyoxylic acid monohydrate 4-Hydroxy-3-methoxyacetophenone Ammonium Hydrazine hydrate... 

The in vitro hydrolysis study, by means of potentiometry, weight loss, SEC and NMR, shows that the degradation mechanism involves simultaneous chain scissions and ester group hydrolysis. Indeed, ester hydrolysis was evidenced by the release of an acidic group as glyoxylic acid hydrate by NMR, or by the drop of pH and the loss of ethanol (weight loss and NMR). The decrease in molecular weight observed by SEC and the presence of small molecules by NMR prove that chain scissions occurred at the same time. 

The ultimate degradation product is glyoxylic acid hydrate which is a Krebs cycle metabolite and allows us to think that PEtG is biodegradable. 

Cycloaddition Reactions. Bis(oxazoline) copper complexes such as 2 (and its hydrated congener) facilitate the [2 + 2] cycloaddition between silylketenes and glyoxylate/pyruvate esters (eq 18). The reaction is tolerant to various silyl substituents and structural variation on the dicarbonyl reactant. 

Miscellaneous. The acrylate provides a synthon for the preparation of 8-Phenylmenthyl Glyoxylate, which is useful for asymmetric ene reactions. Thus ozonolysis and remoeval of the water of hydration produces the glyoxylate in 89% yield (eq 10). 

Proteins respond to the following color tests (a) biuret, pink to purple with an excess of alkali and a small amount of copper sulfate (b) ninhydrin. a blue color when boiled with ninhydrin (triketohydrindene hydrate), which is intensified by the presence of pyridine (c) Millon s test for tyrosine, a brick-F color or precipitate when boiled with mercuric nitrate in an excess of nitric acid (d) Hopkins-Cole test for tryptophan, a violet zone with a salt of glyoxylic acid and stratified over sulfuric acid and (e) xanthoproteic test, a brilliant orange zone when a solution in concentrated nitric acid is stratified under ammonia. Almost all so-called alka-loidal reagents will precipitate proteins in slightly acid solution. 

Addition to C=0. Hydrates of a-ketoaldehydes react selectively at the aldehyde group with allylsilanes under the influence of YbfOTfjj at room temperature. The allylation of aldehydes with allylstannanes is accelerated by benzoic acid." Another method for the synthesis of homoallylic alcohols is by the ene reaction, thus y,6-unsaturated a-hydroxy esters are obtained from glyoxylic esters at room temperature in a catalyzed process. ... 

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