Alkaline isomerization

In 1951, Whistler and Durso reported68 the isolation of epimelibiose by partial, acid hydrolysis of the polysaccharide guaran, followed by charcoal-column fractionation of the products. ThA material was obtained in anhydrous crystalline form from a mixture of methyl and butyl alcohols it had m.p. 201°, [a]26D + 120.9° — +124.6° in 36 hr. (c 2, in water). The yield was 2.2% of the weight of guaran used. Epimelibiose has also been produced72" in crystalline form following the ammonia-catalyzed alkaline isomerization of melibiose. 

Reduction of epimelibiose was reported by French and associates23 73 to give crystalline epimelibiitol, of m.p. 157-8°, which on conversion to the acetate gave crystals of m.p. 122°, [a]21D + 104°(c 0.5, in chloroform). Epimelibiitol was similarly obtained by the reduction of planteobiose29 or of the alkaline-isomerization mixture from melibiose.73 Epimelibiitol and... 

Along with their researches on alkaline isomerization, Lobry de Bruyn and Van Ekenstein21 prepared crystalline D,L-sorbose by evaporating an aqueous solution of the d- and L-isomers. The crystals were later shown to be a racemate compound66 from solubility data. 

Upon reaction with diazomethane or dichloromethane, the phenols can be reetherified. Alkaline isomerization affords the corresponding C-9 epimers (Scheme 47) (704, 70S). 

The two-step mechanism in Scheme 3 accounts for the pH dependence of the monoexponential rate constants observed from neutral pH to pH 10. " The first step in the alkaline isomerization, deprotonation of a titratable group in the native protein, triggers the second step, which is heme iron ligand exchange. This minimal kinetic mechanism does not consider five-coordinate intermediates or multiple alkaline conformers. Biphasic behavior observed in pH-jump experiments above pH 10 suggests the formation of a transient HS heme intermediate in ferricyt c from... 

Reviews on the subjects of the composition of reducing sugars in solution, hydrophobic nature of some sugar derivatives, and aspects of the commercial chemical conversion of glucose, e.g. alkaline isomerism, oxidation, and degradative oxidation, have appeared. 

The most convenient source of conjugated diene acids is via the dehydration of castor oil (Section 3.3.4) by heating ( 250°C) in the presence of an acidic catalyst. The product is complex and the dienes produced from ricinoleate are both conjugated (mainly A9,ll) and non-conjugated (mainly A9,12) in the proportion 1 3 or 4. Several configurational isomers are produced and double-bond migration complicates the product further. Alkaline isomerization of linoleic-rich oils also produces conjugated dienes (A9,ll and A10,12) but these processes have not proved to be of commercial value. 

Today, the synthesis of CLA may foUow various ways it can be achieved by alkaline isomerization, by dehydration of methyl ricinolate, from methyl santalbat or soybean oil, by chemoenzymatic or heterogenous catalysis, by the action of microorganisms or through multistep conventional reaction sequences. A short summary will be given here. 

Several papers have reported the preparation of CLA isomers labeled with carbon isotopes. In aU cases, the labeled carbon atom was located on the carboxylic position. It should also be pointed out that recent preparations of unlabeled (9Z,llE) and (10 ,12 conjugated linoleic acid isomers in their highly purified form were accomplished by alkaline isomerization of (9Z,12Z) linoleic acid followed by selective lipase-catalyzed fractionation (16-18). These procedures may be used for the production of labeled (9Z,llE) and (10E,12Z) CLA because analogs of hnoleic acid labeled with carbon 13 or carbon 14 are commercially available. 

Plasma Cholesterol Fatty Acids in Human Subjects as Determined by Alkaline Isomerization and by Gas Chromatography... 

Early attempts at description of the changes in lipid composition included a diminished degree of unsaturation in deficient animals, indicated by a decrease of the iodine value of tissue lipids. When alkaline isomerization technique became available for measurement of polyenoic acids, the deficient animal was found to have a diminished content of dienoic acid and tetraenoic acid but an enhanced content of trienoic acid (Rieckehoff et al., 1949). Through supplementation with single fatty acids, it was discovered that 1in-oleic acid induced increases in tetraenoic acid (arachidonic acid) but that linolenic acid induced increases in pentaene and hexaene acids (Widmer Holman, 1950). These experiments prompted more elegant ones in the laboratories of Mead and Klenk in which the metabolism of linoleic acid to arachidonic acid, linolenic acid to penta-enoic and hexaenoic acids, and oleic to eicosatrienoic acid were described in detail (Mead, 1971). 

Hansen and his co-workers undertook a long term massive study of essential fatty acid phenomena in infants. In a clinical study of 428 infants, who were fed with five different dietary formulae, they found differences in the dienes, trienes, tetraenes, pentaenes and hexaenes measured by alkaline isomerization. They also found that the content of linoleic acid in the proprietary formulae varied... 

Holman Greenberg (1953) reported the content of polyenoic acids of lamb, swine and beef determined by alkaline isomerization and ultra-violet spectrophometry. In testis of lamb 15.6% of the fatty acids were hexaenoic and 10.3% were tetraenoic in testis of hog 1.5% were hexaenoic and 8.8% were tetraenoic in testis of beef 5.8% were tetranoic acids. Later, indirect evidence was obtained by Cole (1956) suggesting the presence of large amounts of highly unsaturated fatty acids in the testis of the golden hamster. 

If fragmentation and recombination of trioses is occurring during the alkaline isomerization of the hexoses, branched-chain hexoses (not yet isolated) are also to be expected. Dihydroxyacetone undergoes aldol condensation with itself under the influence of dilute sodium hydroxide to, among other products, dendroketose (95). 

Preparation (4, 4S). D-Ribose may be synthesized from D-arabinose by alkaline isomerization, by the glycal synthesis, or through the pyridine-catalyzed epimerization of D-arabonic acid followed by reduction. The sugar also has been prepared by the oxidative degradation of calcium D-altronate (44) and by the nitromethane synthesis from D-erythrose (4 ). 

Preparation. The sugar may be prepared by charcoal-column fractionation of the partial acid hydrolysis products of guaran (4 ) and by the alkaline isomerization of melibiose ( S). 

Planteobiose is synthesizedfrom melibiose by alkaline isomerization 84) and by the action of Acetobacter svboxydans on epimelibiitol 85). 

The stopped-flow technique proved to be more difficult to a-dapt. In this paper we describe an instrument which has been used for some time in our laboratory (5). We report results on the formation of intermediates in chymotrypsin (CT), on the formation of the salt bridge in CT and on the alkaline isomerization of cytochrome c (Cyt). 

CLA produced by alkaline isomerization always contains a mixture of positional and geometric isomers, but the number and position of these can be limited by optimizing the processing conditions. 

Conjugated linoleic acid (CLA) is a collective term for positional (9,11 and 10,12) and geometric (trans,cis cisjrans cis,cis and trarts,tram) isomers of octadecadienoic acid (Cl8 2) with a conjugated double bond. Synthetic CLA, prepared from linoleic acid by alkaline isomerization, exhibits potent anticarcinogenic activities in several carcinogen-induced animal models 1-4) and cytotoxicities for several cancer cell lines (5-5). Other biological activities, such as immune stimulation (P), body fat reduction 10,11 modulation of cholesterol content 12) and growth stimulation 13) were also reported. 

CLA, mainly composed of 47% tram-l0,cis-l2 CLA and 45% cis-9,tram-11 CLA, was synthesized from linoleic acid by alkaline isomerization and methylated with 4% sulfuric acid/methanol solution as described by Park et al. 

A new kinetic model for the alkaline isomerization and degradation of monosaccharides has been presented. Computer simulations using the model fit the experimental data and allow determination of all relevant rate constants. The rate limiting ste appears to be enolization for both isomerization and degradation. The mechanism of redox reactions between lead hydroxide and 3-0-methyl-D-glucose has been studied by quantum mechanical calculations. The calculations show that there is a redistribution of electron density in both systems which favours the formation of a carboxyl group in the C(1)-G(3) part of the aldose. 

The distribution pattern of isohumulone, obtained by alkaline isomerization of humulone, showed that the bands were about 15% broader than the calculated curves... 

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