A . P. G . Kieboom et al. /Aspects of the chemical conversion of glucosecarbohydrate chemistry. Moreover, there is still substantial progress in the science and technology of non--enzymic procedures, which are more generally applicable than enzymatic isomerizations. For instance, the industrial isomerization of lactose into lactulose occurs in aqueous medium with base as the catalyst334, since there is no enzyme system developed as yet for this conversion. The classical paper of Lobry de Bruyn and Alberda van Ekensteid on the interconversion of glucose, fructose and mannose in alkaline solution has been followed by numerous studies on this subject. Enolization is generally accepted6 to be an important first step in the isomerization reaction in alkaline medium as well as in the concomitant degradation reactions, e.g. p-C-0 and p-C-C bond fission. The enediol anion as common intermediate is depicted in Scheme 2.
fructose anionThe enediol anion is intuitively considered to exist predominantly in the (2)-configuration, i.e. with the two oxygens in cis-position, with rapid transfer of the hydrogen between the two oxygens. For the interconversion of glucose, fructose and mannose a mechanism has been proposed' which is based on the principle of least motion and which comprises the following features: ( i j fast equilibrium between cyclic sugar anions and their pseudo-cyclic carbonyl structures, as evidenced by I3C NMR spectroscopy8, (iij formation of the enediol anion by a rate-determining, intramolecular proton shift from C-2 (or C-1 for fructose) to the original ring oxygen, leading to pseudo-cyclic (Z)-enediol anions, and (iii) reversal of process (iij, leading, after conformational changes of the enediol anion species, to isomerization. See Scheme 3 for the molecular picture. glucose anion -e x o > u mannose anion _ I 0' enediol anion degradation products Scheme 2. de Bruyn-Alberda van Ekenstein rearrangement.