Aldehydes periodate oxidation

The size of the rings were subsequently confirmed by C. S. Hudson and colleagues by using periodate oxidation and the determination of the amount of periodate consumed and the nature of the oxidized products [16,17]. It was shown that periodate oxidation is stoichiometric for the cleavage of carbon-carbon bonds whose carbons each have a hydroxyl group. The oxidation cleaves the bond with one periodate and produces two aldehydes. Periodate oxidation of a carbon bond... 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

The synthesis of 11-oxaprostaglandlns from o-glucose uses the typical reactions of gl cofuranose diacetonide outlined on p. 267. Reduction of the hemiacetal group is achieved a thioacetal. The carbon chains are introduced by Wittig reactions on the aldehyde grou] which are liberated by periodate oxidation and laaone reduction (S. Hanessian, 1979 G Lourens, 1975). 

Dissolve an aldehyde-containing macromolecule to be modified (i.e., a periodate-oxidized glycoprotein) in 0.01M sodium phosphate, 0.15M NaCl, pH 7.4, containing ImM EDTA. A suitable concentration range for a protein is l-10mg/ml. 

Figure 1.107 The N-terminal aldehyde group on a peptide formed from periodate oxidation of serine or threonine residues can be conjugated with a hydrazide-containing molecule to produce a hydrazone bond.

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. 

Protein molecule containing periodate-oxidized polysaccharides (having aldehyde groups)... 

Bis-hydrazide-containing molecules also can be used to activate soluble polymeric sub-stances-containing aldehyde groups. For instance, dextran may be periodate oxidized to create numerous formyl functionalities on each molecule. Subsequent reaction with a homobifunctional hydrazide in large excess results in a hydrazide-activated polymer having multivalent-binding capability toward aldehydes or ketones (Chapter 25, Section 2.2). Insoluble support matrices suitable for affinity chromatography have been activated in a similar fashion to create the hydrazide derivative (O Shannessy and Wilchek, 1990). 

The carbonyl-reactive group on these crosslinkers is a hydrazide that can form hydrazone bonds with aldehyde residues. To utilize this functional group with carbohydrate-containing molecules, the sugars first must be mildly oxidized to contain aldehyde groups by treatment with sodium periodate. Oxidation with this compound will cleave adjacent carbon-carbon bonds which possess hydroxyl groups, as are abundant in polysaccharide molecules (Chapter 1, Sections 2 and 4.4). 

Figure 5.12 MPBH reacts with sulfhydryl-containing molecules through its maleimide end to produce thioether linkages. Its hydrazide group then can be used to conjugate with carbonyl-containing molecules (such as periodate-oxidized carbohydrates that contain aldehydes) to give hydrazone bonds.

Figure 9.26 AMCA-hydrazide can be used to label aldehyde-containing molecules, such as periodate-oxidized carbohydrates.

The hydrazide derivative of AMCA can be used to modify aldehyde- or ketone-containing molecules, including cytosine residues using the bisulfite activation procedure described in Chapter 27, Section 2.1. AMCA-hydrazide reacts with these target groups to form hydrazone bonds (Figure 9.26). Carbohydrates and glycoconjugates can be labeled specifically at their polysaccharide portion if the required aldehydes are first formed by periodate oxidation or another such method (Chapter 1, Section 4.4). 

Figure 9.48 A cyanine dye containing a hydrazide group can be used to label glycans at their reducing end or other reducing sugars, forming a hydrazone linkage. Glycoproteins also can be labeled after periodate oxidation to form aldehyde groups.

Figure 14.19 Aldehyde-containing molecules, such as periodate-oxidized carbohydrates or glycoproteins, can be coupled to hydrazide-particles to form a hydrazone bond. This bond can be further stabilized by reduction...

Figure 18.19 Biotin-PEG4-hydrazide is a hydrophilic biotinylation reagent that can be used to modify glycans or carbohydrates at their reducing end or after periodate oxidation to create aldehydes.

The following protocol describes a method for the periodate oxidation of a glycoprotein followed by biotinylation of the resultant aldehydes using hydrazide-PEG4-biotin. Chapter 1, Section 4.6 describes an alternative protocol for the modification of glycans at their reducing ends with hydrazide compounds. 

Figure 20.14 Periodate oxidation of HRP creates aldehyde groups on the carbohydrate chains of the enzyme. Reaction with a Fab fragment then may be done using reductive amination to produce a lower-molecular-weight complex than would be obtained using intact IgG antibodies.

Hydrazide derivatives also may be prepared from a periodate-oxidized dextran polymer or from a carboxyl-containing dextran derivative by reaction with te-hydrazidc compounds (Chapter 4, Section 8). A hydrazide terminal spacer provides reactivity toward aldehyde- or ketone-containing molecules. Thus, the hydrazide-dextran polymer can be used to conjugate specifically glycoproteins or other polysaccharide-containing molecules after they have been oxidized with periodate to form aldehydes (Chapter 1, Section 4.4). 

Hydrazide groups can react with carbonyl groups to form stable hydrazone linkages. Derivatives of proteins formed from the reaction of their carboxylate side chains with adipic acid dihydrazide (Chapter 4, Section 8.1) and the water-soluble carbodiimide EDC (Chapter 3, Section 1.1) create activated proteins that can covalently bind to formyl residues. Hydrazide-modified enzymes prepared in this manner can bind specifically to aldehyde groups formed by mild periodate oxidation of carbohydrates (Chapter 1, Section 4.4). These reagents can be used in assay systems to detect or measure glycoproteins in cells, tissue sections, or blots (Gershoni et al., 1985). 

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... 

This sequence is exemplified by the further reaction of the aldehydic substance XI, obtained by the periodate oxidation of a representative carbohydrate polymer. 

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