Epimerization, of aldoses

Lobry de Bruyn-van Ekenstein transformation. Isomerization of carbohydrates in alkaline media, considered to embrace both epimerization of aldoses and ketoses and aldose-ke-tose interconversion. 

The Lobry de Bruyn-Alberda van Ekenstein transformation has usually been considered to embrace both epimerization of aldoses and ketoses and aldose-ketose isomerization. Actually, Lobry de Bruyn and Alberda van Ekenstein observed all three reactions, so that an experimental basis for defining the transformation has existed from almost the time of its first recognition. 

It is noteworthy that metallomicelles of Ni(II) complexes with long-chain N-al-kylated ethylenediamine ligands catalyze the epimerization of aldoses in an aqueous dispersion [24]. A reexamination of the effect of metallomicelles on the hydrolysis of phosphate and carboxylate esters was given by Scrimin et al. [25], Acceleration in second-order reactions are often to interpret as a local concentration increase of the reactants. The catalytic effect of metallosurfactants in enzyme-related reactions has been investigated by Nolte s working group [26], also carefully considering the assembly structure [27]. The wide field of artificial enzymes was recently reviewed by Murakami et al. [28]. 

The C-2 epimerization of aldoses promoted by Co(II) N,N,N -trimethylethylenediamine complexes has been shown, by use of C-labeUed substrates, to involve a skeletal rearrangement. D-[l- C]glucose, for example, gave D-[2- C]mannose. D-Fructose was isomerized to hamamelose [2-C-(hydroxymethyl)-D-ribose] by Ni(II) N,N -diethylethylene-diamine. The equilibrium mixture contained 29% of the branched component. ... 

The essentiality of the OH group at C-2 for the epimerization of aldoses is obvious. The same is valid for the carbonyl group of aldoses since alditols do not undergo epimerization changes in molybdic acid [20,21]. 

The rate of the molybdate-catalyzed epimerization reaction is highest in the pH range 1.5-3.5 and is up to 20 times higher than at pH 5.9, where the cyclic species of aldoses form the most stable molybdate complexes [21,22]. At pH higher than 6.0 and below pH 0.1 the molybdate-catalyzed epimerization of aldoses does not occur [22,23]. 

As mentioned above, the coordinating behavior of nickel(II) with carbohydrates has been studied in detail [30-38]. Yoshikawa and Yano clarified that the nickel complexes that coordinate ethylenediamine have the ability to isomerize aldoses into their corresponding epimers at C-2 along with stereospecific rearrangement [39,40,43]. They applied the coordinating abihties of nickel, diamine and sugar in a sophisticated reaction, and established a distinct reaction system that is different from the traditional enediol epimerization of aldoses by alkaline solution. 

In order to develop a suitable catalytic system for nickel/diamine complex assisted epimerization of aldoses, various kinds of diamines were prepared and their influences on epimerization studied [44 a, c]. One of the most effective chemical alterations is W-alkylation of ethylenediamine. Due to the variety of alkyl chain lengths and degree of alkylation around nitrogen atoms, the stability of the complexes should be profoundly changed according to the steric interactions between the sugar and the ligand in the complex. 

Looking at it from another angle, it would be feasible to state that there are two prerequisites to accompHsh the epimerization of aldoses by a nickel complex. As the first requirement, the Ni(II)/diamine complex must have the abiUty to incorporate sugar and lead to the ternary complex. In this context, simple diamines such as free ethylenediamine and methylated ones have the potential to produce the ternary complex. As the second prerequisite, the resulting ternary complex must be appropriately unstable to undergo a mutation and a transition in the complex. 

We carried out an extensive survey of the C-2 epimerization of various aldoses and ketoses [44b]. Because of the variety of the possible aldose configurations, the stability of the complexes should vary accordingly. In order to understand the effects of configuration on the epimerization of aldoses, a variety of aldohexoses, aldopentoses, and 6-deoxyaldohexose were studied along with four ketoses. The stereospedfic and regiospecific rearrangement of these ketoses will be studied in detail in Sect 4. 

The results for the rearrangement of D-fructose (4) into D-hamamelose (5) and L-sorbose (7) into 2-C-hydroxymethyl-L-lyxose (8) are summarized in Table 7. Each reaction was conducted in a manner similar to the epimerization of aldoses as shown in Scheme 1, except for the reaction temperature (30 °C) and the reaction time (40 min), employing methanol as the solvent. 

In a discussion on the influence of the diamine structure on the rearrangement of ketoses, information obtained from the epimerization of aldoses could be of interest. As pointed out in the context of the reaction mechanism, when a... 

In this section, the effect of aggregates such as metallomicelles comprised of nickel and hydrophobic diamines on the epimerization of aldoses is outhned. A homologous series of nickel/ethylenediamine complexes of various N,N-dime-thyl-N -alkylethylenediamines (l,l,n -en) was prepared and examined [64], The influence of the hydrophobicity of the Hgand on the epimerization in aqueous media was assessed. The objective of this work was to clarify why differences in hydrophobicity affect the outcome of the epimerization and to characterize the nature of the aggregative metallomicelle. 

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