Hydroxy acids, oxidation, lead

Periodic acid reacts well in aqueous solution. Usually, if the reactant has to be run in organic solvents, lead tetraacetate is used as the reagent. Interestingly, periodic acid will not act on a-keto acids or a-hydroxy acids whereas lead tetraacetate wiU. The corresponding reactions are actually oxidative decarboxylations. 

A contrasting mode of flavoprotein reactivity with an acetylenic inactivator occurs in the reaction of 2-hydroxy-3-butynoate (13, Fig. 15) with a number of a-hydroxy acid oxidizing enzymes. This process is exemplified by the inactivation of L-lactate oxidase from Mycobacterium smegmatis, an enzyme which catalyzes the oxidative decarboxylation of lactate to yield acetate, carbon dioxide, and water (Walsh, 1979, p. 408). Incubation of 13 with lactate oxidase leads to inactivation of the enzyme with a partition ratio that varies from 110 in the... 

PurpurogaHin (5), a red-brown to black mordant dye, forms from electrolytic and other mild oxidations of pyrogaHol (1). The reaction is beHeved to proceed through 3-hydroxy-(9-benzoquinone (2) and 3-hydroxy-6-(3,4,5-trihydroxyphenyl)-(9-benzoquinone (3). The last, in the form of its tautomeric triketonic stmcture, represents the vinylogue of a P-diketone. Acid hydrolysis leads to the formation of (4), foHowed by cyclization and loss of formic acid... 

Hydroxyisophthalic acid has been prepared by oxidizing 2-hydroxy-3-methylbenzoic acid with lead dioxide, by cleaving the ether group of 2-methoxyisophthalic acid with hydriodic acid, and by hydrolyzing 2-iodoisophthalic acid with alcoholic sodium hydroxide. ... 

Lead tetraacetate fragmentation has not been applied to the 20-hydroxy-18, 20-cyclo steroids. However, preferential cleavage of the 17,20-bond would be expected, as was observed in the chromic acid oxidation of a saturated 20-hydroxy-18,20-cyclo steroid in hot acetic acid which affords the 18-acetyl-17-ketone in 50-60% yield. 

The application of this addition to aminomethylene ketones provides a convenient synthesis of monoamides of pimelic acid (508). It should be noted that the corresponding oxidation of hydroxy methylene cyclohexanone leads to ring contraction and formation of cyclopentanoic acid. 

Triazine 4-oxides 55 react with phenols (phenol, 2,6-dimethylphenol, resorcinol, 4-hexyh esorcinol) in trifluoroacetic acid in a similar way, yielding intermediate (T -adducts 5-hydroxyphenyl-4-hydroxy-4,5-dihydro-l,2,4-triazines 61. Subsequent oxidation leads to the corresponding 5-hydroxyphenyl-l,2,4-triazine 4-oxides 62 (97MC116). 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

Hydroxylamine-O-sulfonic acid for N-amination of pyridine, 43, 1 Hydroxylation of indene, 41, 53 2-Hydroxy-3-methylbenzoic add, oxidation to 2-hydroxyisophthalic acid by lead dioxide, 40, 48 Rydroxymethyleerrocene. 40, 52... 

The ligand group can be introduced either on the meso or on the /5-pyrrole position of the porphyrin ring, but the synthesis of the meso-functionalized derivatives is easier and has been more widely exploited. Balch (50-53) reported that the insertion of trivalent ions such as Fe(III) (32) and Mn(III) (33) into octaethyl porphyrins functionalized at one meso position with a hydroxy group (oxophlorins) leads to the formation of a dimeric head-to-tail complex in solution (Fig. 11a) (50,51). An X-ray crystal structure was obtained for the analogous In(III) complex (34), and this confirmed the head-to-tail geometry that the authors inferred for the other dimers in solution (53) (Fig. lib). The dimers are stable in chloroform but open on addition of protic acids or pyridine (52). The Fe(III) octaethyloxophlorin dimer (52) is easily oxidized by silver salts. The one-electron oxidation is more favorable than for the corresponding monomer or p-oxo dimer, presumably because of the close interaction of the 7r-systems in the self-assembled dimer. 

In the oxidative lipid metabolism, an intermediary a-hydroperoxy acid is formed by a-oxidation of the corresponding fatty acid [82, 83]. Presumably, peroxidase-catalyzed reduction of the hydroperoxide leads to enantiomerically pure (R)-2-hydroxy acids [84]. 

Optically active aldehydes are available in abundance from amino and hydroxy acids or from carbohydrates, thereby providing a great variety of optically active nitrile oxides via the corresponding oximes. Unfortunately, sufficient 1,4- or 1,3-asymmetric induction in cycloaddition to 1-alkenes or 1,2-disubstituted alkenes has still not been achieved. This represents an interesting problem that will surely be tackled in the years to come. On the other hand, cycloadditions with achiral olefins lead to 1 1 mixtures of diastereoisomers, that on separation furnish pure enantiomers with two or more stereocenters. This process is, of course, related to the separation of racemic mixtures, also leading to both enantiomers with 50% maximum yield for each. There has been a number of applications of this principle in synthesis. Chiral nitrile oxides are stereochemicaUy neutral, and consequently 1,2-induction from achiral alkenes can fully be exploited (see Table 6.10). 

Trimethylcyclopentanone has been prepared by the oxidation of 1-hydroxy-2,4,4-trimethylcyclopentanecarboxylic acid with lead dioxide in sulfuric acid,3 by the hydrogenation of 2,4,4-trimethyl-2-cyc.lopentenone, 4 5 by the Clemmensen reduction of dimethyldihydroresorcinol,6 7 by the distillation of powdered 2,4,4-trimethyladipic acid with sodium hydroxide,8 and by the saponification and decarboxylation of ethyl 2-keto-l,4,4-tri-mcthylcylopentanecarboxylate.9 10 The rearrangement of iso-phorone oxide 11 appears to represent the optimum combination of favorable yield and convenient procedure. 

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