Lobry de Bruyn-van Ekenstein rearrangement

Endiols (4.80) can isomerize into other saccharides in the Lobry de Bruyn-van Ekenstein rearrangement. Thus, D-glucose (5.4) can isomerize into mannose (5.81) and fructose, (5.1) accompanied by a small amount of D-psicose (5.83). Alkaline medium provides isomerization to disaccharides, which turn from aldoses into ketoses, as shown for lactose (5.7b) isomerized to lactulose (5.84). 

By heating of foodstuffs, aldoses and amino acids form N-glycosides, which lead to Amadori products by an Amadori rearrangement (Mario Amadori (1886-1941), Italian chemist). The mechanism is analogous to that of the Lobry de Bruyn-van Ekenstein rearrangement (Cornehs Adriaan Lobry van Troosten-burg de Bruyn (1857-1904) and Willem Alberda van Ekenstein (1858-1937) were chemists from the Netherlands). 

Lactulose is found in heated milk products. It is a little sweeter and clearly more soluble than lactose. For example, condensed milk contains up to 1% of lactulose, corresponding to an isomerization of ca. 10% of the lactose present. The formation proceeds via the Lobry de Bruyn-van Ekenstein rearrangement (cf. 4.2.4.3.2) or via SchiffhasQ. Traces of epilactose (4-0-P-D-glacto-... 

This reaction is related to the Lobry de Bruyn-van Ekenstein transformation of aldoses involving the rearrangement of A-alkylamino-D-glucopyranosides into 1-alkylamino-l-deoxy-D-fructoses. ... 

This reaction was first reported by Lobry de Bruyn in 1895, and explored extensively by Lobry de Bruyn and Alberda van Ekenstein. It is the reciprocal interconversion of carbohydrates into their isomers in an alkaline solution through the enediolic intermediate. The name of reaction given here is probably the only one time the full name of the people who discovered such reaction. It is known as the Lobry de Bruyn-Alberda van Ekenstein rearrangement, Lobry de Bruyn-Alberda van Ekenstein transformation, Lobry de Bruyn-Albreda van Ekenstein C-2 epimerization, or Lobry de Bruyn-van Ekenstein transformation. ... 

For the preparation of 2 by aqueous, alkaline hydrolysis of the lactone ring in 4, precautions against Lobry de Bruyn-Alberda van Ekenstein rearrangements,100 and even against decomposition101 of... 

Aldoses generally undergo benzilic acid-type rearrangements to produce saccharinic acids, as well as reverse aldol (retro-aldol) reactions with j3-elimination, to afford a-dicarbonyl compounds. The products of these reactions are in considerable evidence at elevated temperatures. The conversions of ketoses and alduronic acids, however, are also of definite interest and will be emphasized as well. Furthermore, aldoses undergo anomerization and aldose-ketose isomerization (the Lobry de Bruyn-Alberda van Ekenstein transformation ) in aqueous base. However, both of these isomerizations are more appropriately studied at room temperature, and will be considered only in the context of other mechanisms. 

The main reactions are 1,2-enolisation (Lobry de Bruyn-Alberda van Ekenstein rearrangement, cf. Amadori rearrangement), dehydration to furfurals, and fission (see ref. 563). 

In weakly alkaline solutions aldoses and ketoses undergo rearrangements. An example is the Lobry de Bruyn -Alberda van Ekenstein transformation of... 

The Amadori rearrangement has some features of the Lobry de Bruyn-Alberda van Ekenstein transformation, as can be seen from the ammono analogy to sugar enolization formulated in Part 2 of this Section. Both reactions occur in basic media, and each doubtless involves 1,2-enolization of the sugar. However, the Amadori rearrangement proceeds by acceptance of a proton from the acid catalyst, whereas the Lobry de Bruyn Alberda van Ekenstein transformation proceeds by delivery of a proton to the base catalyst. Aside from what may be argued as to the enolization mechanism, there are other important differences. 

It is of interest that, in 1882, lime-water treatment of lactose was found to yield the insoluble calcium a -D-isosaccharinate, a rearrangement product of the n-glucose component, and, in 1896 and 1899, Lobry de Bruyn and Alberda van Ekenstein" observed that treatment of lactose with either lead hydroxide or potassium hydroxide liberated n-galactose. Kiliani established the structure of the saccharinate as that of a 3-deoxy-2-C-(hydroxymethyl)pentonic acid and, had the mechanism of its formation been understood (see p. 188), this would have been sufficient evidence... 

Lipides, 238, 239, 241-243, 261 Lipidosis, 239, 242, 243 Lobry de Bruyn-Alberda van Ekenstein transformation, 63, 291 acid catalysis of, 79 aldolization in, 77 base catalysis of, 79-81 catalysis of, by metal ions, 81 dealdolization in, 77 dehydration reactions in, 73 enzyme-catalyzed, 66, 70 formation of reductones in, 79 of or-hydroxy aldehydes, 71 mechanism of, 84 of noncarbohydrate a-ketols, 71 non-enzymic, 66, 67, 83 in paper chromatography, 81 rearrangement of carbon chain, 79 scope of, 65 of steroids, 72 use of, for synthesis, 82 Lyxonic acid, 3-deoxy-D-, 300 Lyxose, D-, condensation of, with urea, 218... 

The formose reaction in detail, however, consists of a series of reactions primary self-addition of formaldehyde followed by aldol reaction of products with each odier and with formaldehyde. Cannizzaro and cross-Cannizzaro reactions occur, as well as Lobry de Bruyn-Alberda van Ekenstein rearrangements. Product decomposition (for example, to chromophores) occurs if the reaction conditions are unduly severe. The monosaccharides formed are all dl (racemic), with no optical rotatory... 

Some methods of metal ion-catalyzed chemical and enzymic isomerization (Lobry de Bruyn-Alberda van Ekenstein rearrangement, epimerization at C-2 of aldoses, action of isomerases) of free sugars have been reviewed (136 refs.). ... 

Fig. 1. Lobry de Bruyn - Alberda van Ekenstein rearrangement of sugars in dilute alkali. R = rest of the molecule.

An early application of the Amadori rearrangement reaction was the synthesis of lactulose 51 (Scheme 15) [68]. Reaction of lactose 48 withp-toluidine in pyridine/acetic acid furnished the corresponding rearrangement product 49, which, after catalytic hydrogenolysis to 1-amino-1-deoxyketose 50 and subsequent deamination, gave ketose 51. This was the first alternative approach to lactulose, which had been synthesized via a Lobry de Bruyn - Alberda van Ekenstein rearrangement [69]. 

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