Of periodate oxidation

Oxidation of C9-Amine (3) with Lead Tetraacetate. C9-Amine hydrochloride (53 mg., 0.17 mmole) was dissolved in 0.1 ml. of water and 5 ml. of acetic acid and to the solution was added lead tetraacetate (190 mg., 0.3 mmole) at 16°-18°C. in 10 minutes. Insoluble material was removed by filtration, and the filtrate was dried by lyophilization. The residue was dissolved in 5 ml. of water and the solution was placed on a column of Amberlite CG-50 (ammonium form, 1 x 10 cm.) followed by a similar treatment as described in the case of periodate oxidation. N-Cyano derivative (5.1 mg.) was obtained and proved to be identical with the N-cyano derivative obtained from the periodate oxidation. 

Crystalline triose reductone has been shown (56) by titration with strong base and with iodine, to exist in solution, for practical purposes, entirely as the enol form. In addition, the fact that it reduces exactly three molar equivalents of periodate to give quantitative yields of formic acid and of carbon dioxide indicates that it is also oxidized entirely in this form. However, nothing is known of the rate of enolization of tartronic dialdehyde and the possibility therefore remains that part of it may be oxidized in the dialdehydo form. If this were the case, the results of periodate oxidations would be dependent on the ratio of the rate of enolization of tartronic dialdehyde to the rate of its oxidation by periodate, since the oxidation of triose reductone is, again, for practical purposes, instantaneous. 

It is, in fact, interesting to note that the latter cyclohexanepentol, which has four adjacent cis-hydroxyl groups, reacts slowly with periodate. Perhaps further light will be thrown on this problem when the results of periodate oxidations of dl-1, 2, 3, 5/4-cyclohexanepentol (36), 1, 2, 4, 5/3-cyclohexanepentol (37), and (1 d)-1, 2, 3/4, 5-cyclohexanepentol (38) will be available. 

These oxidants have been used rarely. The kinetics of periodate oxidation of sulphoxides have been studied119,124. In an acid medium the reaction proceeds without catalysis but in alkali a catalyst such as an osmium(VIII) or ruthenium(III) salt is required124. Iodosylbenzene derivatives have also been used for the oxidation of sulphoxides to the sulphone level94,125 (equation 39). In order to use this reaction for the synthesis of sulphones, a ruthenium(III) complex should be used as a catalyst thus quantitative yields are obtained at room temperature in a few minutes. However, column chromatography is required to separate the sulphone from the other products of the reaction. 

Aldehyde-containing macromolecules will react spontaneously with hydrazide compounds to form hydrazone linkages. The hydrazone bond is a form of Schiff base that is more stable than the Schiff base formed from the interaction of an aldehyde and an amine. The hydrazone, however, may be reduced and further stabilized by the same reductants utilized for reductive amination purposes (Chapter 3, Section 4.8). The addition of sodium cyanoborohydride to a hydrazide-aldehyde reaction drives the equilibrium toward formation of a stable covalent complex. Mallia (1992) found that adipic acid dihydrazide derivatization of periodate-oxidized dextran (containing multiple formyl functionalities) proceeds with much greater yield when sodium cyanoborohydride is present. 

AMCA-hydrazide is soluble in DMSO or DMF and may be dissolved as a concentrated stock solution in either of these solvents prior to the addition of a small aliquot to an aqueous reaction medium. The solid and all solutions made from the fluorophore must be protected from light to avoid photo-decomposition. Prepare the stock solution fresh immediately before use. A suggested protocol on the use of this fluorescent probe may be obtained from the following method on the labeling of periodate-oxidized IgG. Optimization may be necessary to achieve the best level of fluorescent modification (F/P ratio) for a particular application. 

Conjugation of Periodate-Oxidized HRP to Antibodies by Reductive Animation... 

Conjugation of Periodate-Oxidized Antibodies with Amine orHydrazide Derivatives... 

Kobayashi, M., and Ichishima, E. (1991) Application of periodate oxidized glucans to biochemical reactions./. Carbobydro Chem. 10, 635-644. 

The next step in the development of periodate oxidation was made by Nicolet and Shinn.8 They applied periodate oxidation to a series of a-amino acids, and found that those containing the 2-hydroxyamine structure are almost instantaneously oxidized. For such an oxidation to proceed rapidly, the amine could not be tertiary. An a-hydroxy A-acylamine was attacked very slowly, if at all. Only a small number of compounds were investigated. 

More successful applications of periodate oxidation to substituted sugars were made employing the sugar phosphates and phosphoric acids,63 66 the chloraloses, 62 70 the benzyl ethers of sugars,71 72 a dimethyleneoxy sugar,73... 

The application of periodate oxidation to a problem can best be considered in terms of an approach from two separate standpoints. The first generally involves the application of analytical techniques to semimicro quantities of material, and sometimes suffices to yield the desired information. After performing this preliminary, analytical investigation, the second or preparative phase may be undertaken. This entails use of much larger amounts of material, with the intention of isolating the end products of oxidation. If these are obtained, their properties should serve to confirm the results of the preliminary, analytical work and, if this is proved correct, the method is then available as a route to the desired synthetic compound. 

Since aldehydes are notoriously polymerizable and difficult to manipulate, the products of periodate oxidation are oftentimes further oxidized, with hypohalite, to carboxylic acids, or are reduced to the corresponding alcohols. Oxidation has been more usually employed than reduction, since acids frequently form crystalline salts and other conveniently prepared derivatives. A process of oxidation of these aldehydic products by hypo-bromite, in the presence of barium carbonate or strontium carbonate, was developed and used extensively by Hudson and his coworkers.107 110 194-199,90s Their method can best be illustrated by an example the further oxidation of the dialdehyde, VI, shown previously (see p. 16) to be obtained by the oxidation of the methyl a-D-aldohexopyranosides. The isolation of... 

The reaction of these aldehydes, derived from periodate oxidation, with carbonyl reagents has also been investigated. Studies 147 148 were made on oxidized laminarin, a (1 —> 3)-linked polysaccharide, in which only the terminal residues had been oxidized. The addition of phenylhydrazine acetate detached the remainder of the terminal residue as glyoxal phenyl-osazone. When the aldehydic compounds derived from the periodate oxidation of raffinose and trehalose818a were reacted with p-nitrophenylhydrazine, the authors were surprised to find that one molecule of oxidized raffinose, containing six aldehydic functions, reacts with only three molecules of the reagent, and that the four aldehydic functions of the oxidized trehalose molecule react with only two. The reactions of periodate-oxidized carbo-... 

The use of water or of an aqueous solvent as the reaction medium is a characteristic of periodate oxidation, as performed in this field. This situation is ideal for most work on carbohydrates, but imposes on applications to other fields of organic chemistry a limitation which, nevertheless, has been partially circumvented in a number of ways. 

This article has not been in any sense an attempt to enumerate all of the known examples of periodate oxidation of carbohydrates. It has endeavored to explain and illustrate as many of the different types of periodate... 

The ultraviolet absorption spectra of compounds II from D-glucose and XI from D-fructose show an absorption band at 250 m/j, in accordance with their furan character.9 The product of periodate oxidation (V) and the dimethyl ester of the derived dicarboxylic acid (III) absorb at 285 and 262 m/i, respectively. The anhydrides of the condensates, XXXIV, do not exhibit selective absorption in the ultraviolet region, but the product of their oxidation (XXXVI) with periodic acid shows8 a band at about 270 m/i. 

XVIII has now been excluded,42 since the methyl glycoside of the sugar reacts rather rapidly with one mole of periodate per mole furthermore, in contrast to the behavior of mycaminose (XXI), no moiety with one carbon atom less has been isolated from the products of periodate oxidation. Oxidation of mycarose with hypoiodite affords a crystalline lactone with the empirical formula C7H12O4 this observation eliminates the possibility of the keto structure XX. Thus, mycarose appears to be a 2,6-dideoxy-3-C -methylhexose (XIX). In the original compound, the isovaleryl group must be esterified to the alcohol function at C4, since the methyl glycoside isovalerate obtained from carbomycin is only attacked by periodate after alkaline hydrolysis. 

Pacsu4 5 has suggested a structure for starch involving a small number of non-cyclic hemiacetal linkages, the number being presumably sufficient to account for the number of endgroups determined by the methylation method. Halsall, Hirst and Jones6 have commented on this structure, however, and have shown it to be incompatible with the results of periodate-oxidation studies. In addition, these authors pointed out that it would be difficult to explain enzymic hydrolysis and dextrin formation on the basis of such a structure. 

Investigations of the lability of the periodate-oxidized product to alkali showed that the pH, during titration of the liberated formic acid, had to be very carefully controlled. Quantitative titration of formic acid, in the presence of all normal oxidation products, was shown to be complete at pH 6.25. (Over-titration, to pH 8.0, reduced the value of average unit chain by 20%.) The effect of contaminating protein on the results of periodate oxidation has also been studied in detail.82 ... 

Table I shows the results of periodate oxidation and methylation applied to amylopectins from various sources. If the percentage of amylose in a whole starch is known, the length of unit chain of the amylopectin component can be calculated from the results of periodate oxidation of the whole starch (see Table II). The length of unit chain appears to depend on the botanical species, but not the variety, from which the starch wras isolated. In the case of tapioca and corn amylopectins, sub-fractionation of these by precipitation with methanol, followed by periodate oxidation, showed the sub-fractions had the same degree of branching as the original amylopectins.71 The action of periodate on whole starches and amylopectins is now so well established and accurate, that it may well completely supersede the methylation technique for pure starches, in view of its many advantages.

Other workers140 have also examined the products derived by hydrolysis of periodate-oxidized xylan. Both wheat straw and com cob xylan, after oxidation and hydrolysis, yield small amounts of L-arabinose and D-xylose. These sugars are obtained even after the xylans have been subjected to extended periods of oxidation. It is concluded that the D-xylose constituted branch points in the xylan. Likewise, the L-arabi-nose molecules must not have been terminal units in a xylan chain but must have been either interior units in the xylan molecule or have constituted an araban-like polysaccharide which is in combination or admixture with the xylan polysaccharide. 

If the products of periodate oxidation are reduced with sodium borohy-dride, polyalcohols are produced which may be readily hydrolysed under mildly acidic conditions and the reaction products can be determined. The identification of these products gives considerable information about the linkages between the polysaccharide components and also their sequence in the overall structure. 

The laboratory procedures and the interpretation of the results of periodate oxidation studies are complicated exercises and this brief account is intended only as a general introduction to the topic and further details, if required, should be sought from a more specific text. 

Exhaustive studies on well-defined systems are rather scarce (4) nevertheless 3 systems thoroughly analyzed by independant research groups are of outstanding interest a) the quaternization of polyvinylpyridines by alkyl halogenides (20-25) b) the chlorination of polyethylene (13,26-28) c) the basic or acid hydrolysis of PMMA (29-31). On the other hand, neighbouring groups effects have been quantitatively taken into account for the kinetic analysis of periodate oxidation of amylose (32,33). 

The effect of pH on the periodate oxidation of seven anilines has been investigated. " The kinetics of periodate oxidation of aromatic amines have been studied. " - " Periodate oxidation of oxalic acid is catalysed by Mn(II). " The reaction of ethane-1,2-diol with periodate has been investigated under a variety of conditions and the results compared with those of earlier work and analogous studies on pinacol. " The 104 ion is the primary reactant, with H5IO6 as a secondary reactant the reverse is true for pinacol. The complex observed in previous work is shown not to be an intermediate, but rather to deactivate the reactants. 

---