John E. Hodge

The Amadori Rearrangement

Publisher Summary This chapter discusses the reaction that is the isomerization of an aldosylamine to a 1-amino-1-deoxy-2-ketose. This rearrangement was named after Amadori by Kuhn and Weygand, for Amadori was the first to demonstrate that condensation of D-glucose with an aromatic amine ( p -phenetidine, p -anisidine, or p -toluidine) would yield, according to experimental conditions, two structurally different isomers, which are not members of an α, β anomeric pair. Amadori did not realize that an isomerization (“rearrangement”) from an aldose to a ketose configuration had occurred. However, he did discern (by change of optical rotation in acid solution) that one isomer is much more labile than the other toward hydrolysis and more susceptible to decomposition on standing in the solid state in air. He recognized correctly that the labile isomer is the N -substituted glucosylamine, but he mistakenly thought that the stable isomer was a compound of the Schiff-base type. Authentic crystalline products of the Amadori rearrangement have so far been obtained only from D-glucose, D-mannose, and 5- O -trityl-D-xylose as the sugar components. Occurrence of the rearrangement (or at least 1, 2-enolization of the N -substituted glycosylamine) was demonstrated indirectly, however, by isolation and characterization of crystalline epimeric hydrogenation products derived from D- and L-arabinose and also from D-xylose.

Amadori compounds: vacuum thermolysis of 1-deoxy-1-l-prolino-d-fructose

Abstract Amadori compounds are important precursors of color and aromas in foods, proline-sugar reactions produce bready aromas in roasted cereals and baked goods. To produce the volatile aroma-compounds, 1-deoxy-1- l -prolino- d -fructose was heated under vacuum, first at 140°, and then at 240°. The distillates were condensed at −70°, and from them 22 compounds were identified by g.l.c.-m.s., p.m.r., i.r. spectroscopy, g.l.c. and synthesis. At 140°, there were major proportions of 6-carbon dehydration products (dihydrofurans, dihydropyrones, pyrones, and a methylcyclopentenolone), lesser proportions of scission compounds (acetic acid and the pyrrolidine amides of formic, acetic, and propionic acids), substituted furfuryl-amines, a diazepine, proline, and pyrrolidines derived from proline. At 240°, the title compound yields more of the pyrrolidine derivatives, maltol, pyrrolidine amides of formic, acetic, and propionic acids, a γ-lactone, and 2-pyrrolino-substituted furans. Product aromas were determined and degradation schemes, based on the isolated products, were formulated.

Preparation and characterization of 1,2,6,2′,3′,4′,6′,hepta-O-acetyl-β-maltose☆

Abstract Acetylation of a slurry of β-maltose monohydrate in cold toluene with acetyl-pyridinium chloride gave 1,2,6,2′,3′,4′,6′-hepta- O -acetyl-β-maltose ( 1 in 70% yield, with octa- O -acetyl-β-maltose as a byproduct. Crystalline 3- O -methyl ( 2 ) and 3- O -phenylcarbamoyl ( 3 ) derivatives of 1 were readily obtained. A deacetylated sample of 2 was shown to yield 3- O -methyl-α,β- d -glucose and α-β- d -glucose after aqueous hydrolysis. To discriminate between the O-3 and O-3′ positions, a second deacetylated 2 was reduced with sodium borohydride and the product methanolyzed, to yield 3- O -methyl- d -glucitol and methyl α,β- d -glucopyranoside; components of the methanolyzate were identified by g.l.c. Deacetylation and methanolysis of 3 gave methyl 3- O -phenylcarbamoyl-α-β- d -glucopyranoside ( 5 ), from which methyl 2,4,6,-tri- O -benzoyl-3- O -phenylcarbamoyl-β- d -glucopyranoside ( 6 was isolated crystalline; synthesis of 6 from 1,2:5,6-di- O -isopropylidene-α- d -glucofuranose proved its structure.

Complexes of carbohydrates with aluminate ion. Aldose-ketose interconversion on anion-exchange resin (aluminate and hydroxide forms)

Abstract Kinetic parameters for aldose and ketose transformations in the d -glucose- d -mannose- d -fructose system at 27° on aluminate resin and hydroxide resin were obtained. On both resins, hydroxide ion functions as the catalyst for isomerization. By forming a complex with d -fructose, resin-bound aluminate ion stabilizes the ketose and permits high yields (up to 72%) of d -fructose from d -glucose. The effect of temperature on d -glucose-to- d -fructose conversion was studied; lower temperatures give the higher maximum yields. Maltose is converted into maltulose in moderately high yield (63%) at 24° on aluminate resin; higher yields are not possible at this temperature because of a marked tendency for maltulose to undergo elimination of d -glucose at C-4.

Complexes of carbohydrates with aluminate ion. Chromatography of carbohydrates on columns of anion-exchange resin (aluminate form)☆

Abstract With water as sole eluant, the retention volumes for carbohydrates on an aluminate-resin column generally decrease in the order: ketoses>aldoses>alditols>methyl glycosides; retention increases with molecular size. Both aluminate ion and hydroxide ion contribute to the chromatographic properties of an aluminate resin. To avoid alkaline degradation and interconversion, which can occur extensively at 25°, chromatography of reducing sugars must be performed both rapidly and at low temperature. A mixture of d -glucose and d -fructose can be completely separated on a short aluminate column.

Dioxolane configuration in diastereoisomeric 1,2-O- and 1,2:4,6-di-O-alkylidene-α-d-glucopyranose derivatives by n.m.r. spectroscopy

Abstract Three related pairs of diastereoisomers, the previously unknown 3,4,6-tri- O -acetyl-1,2- O -ethylidene- and 3- O -acetyl-1,2:4,6-di- O -ethylidene-α- d -glucopyranoses, and the known 3,4,6-tri- O -acetyl-1,2- O -benzylidene-α- d -glucopyranose, were prepared by reduction of intermediate dioxolenium chloride ions with sodium borohydride. Each pair of isomers was separated into its components by preparative t.l.c. Four correlations of n.m.r. parameters with dioxolane configuration were used to assign the structure of each isomer of a diastereoisomeric pair: ( 1 ) Deshielding of the 2′-substituent when endo : ( 2 ) deshielding of H-2 or H-5 by bulky exo or endo 2′-substituents; ( 3 ) larger values of J 2,3 and J 3,4 when a bulky 2′-substituent has an exo orientation; and ( 4 ) the presence of long-range ( 4 J ) coupling of H-2 and H-4 of the pyranose ring only in molecules with a bulky 2′-substituent in an endo orientation. The degree to which the pyranose ring is distorted by the cis -fusion of a dioxolane ring in such derivatives, as well as by endo phenyl, methyl, and proton substituents, is evaluated.

Thermal degradation of 1-deoxy-1-piperidino-d-fructose

Abstract Crystalline 1-deoxy-1-piperidino- d -fructose ( 1 ) was pyrolyzed in a sublimation apparatus at 106° and 0.1 torr. The sublimate-distillate collected consisted of piperidine acetate (43%); two piperidino derivatives of C -methyl reductone (28%); 4-hydroxy-2-piperidino-butanolactone (1.4%); and the piperidine amides of carbonic (6.5%), formic (1.6%), and acetic (5.1%) acids. Trace proportions of other volatile compounds were identified as 4-hydroxy-2,5-dimethyl-3(2 H )-furanone; 2,5-dimethyl-3-piperidinofuran; 2-acetyl-3-piperidinofuran; 2-acetyl-3-piperidino-4,5-dihydrofuran; and the piperidides of glycolic, lactic, and butyric acids. Under the same pyrolysis conditions the piperidino C -methyl reductones isolated were degraded to carbonic, formic, and acetic piperidides. After separation of these compounds by preparative g.l.c., the products were identified by mass, i.r., and p.m.r. spectra; almost all were positively identified with compounds separately synthesized. The results indicate that piperidine is eliminated from C-1 and recombines at C-3 of the hexose carbon-skeleton before the primary C 4 , C 2 fission occurs.

O-ethylidene-D-allopyranoses: 1,2-O-,1,2:4,6-, and 2,3:4,6-di-O-ethylidene derivatives☆

Abstract Solutions of 1,2-O-acetoxonium chlorides derived from O-acetylated D -allopyranose derivatives were treated with sodium borohydride to give three pairs of previously unknown 1,2-O-ethylidene-α- D -allopyranose diastereoisomers: 3,4,6-tri-O-acetyl-1,2-O-ethylidene-α- D -allopyranoses; 4,6-di-O-acetyl-3-O-benzyl-1,2-O-ethylidene-α- D -allopyranoses; and 3-O-benzyl-1,2:4,6-di-O-ethylidene-α- D -allopyranoses. Examples of a second class of novel O-ethylidene- D -allopyranoses, the diastereoisomeric methyl 2,3:4,6-di-O-ethylidene-α- D -allopyranosides, were prepared by treating methyl 4,6-O-benzylidene-α- D -alloside with acetaldehyde-sulfuric acid. Assignments of dioxolane ring configurations and pyranose conformations were made by n.m.r. analyses.

Determination of 3-deoxy-D-erythro-hexosulose (3-deoxy-D-glucosone) and other degradation products of sugars by borohydride reduction and gas-liquid chromatography

Abstract Quantitative analysis of 3-deoxy- D - erythro -hexosulose (1) among other degradation products of sugars, by gas-liquid chromatography (g.l.c) of its pertrimethylsilyl (TMS) ethers, was not feasible because the multiplicity of tautomeric forms gave numerous peaks. However, borohydride reduction of the complex aldosulose gave only the two expected 3-deoxyhexitols, and these were readily separated from other reduced degradation products of sugars by g.l.c. of their TMS ethers. Relative retention times ( T R ) of TMS ethers of alditols and saccharinolactones (C-2-C-6) likely to arise through alkaline degradation and browning reactions of sugars were determined on two columns to provide a method for analyzing complex mixtures of labile degradation products from sugars. Plots of T R vs. molecular weight of the TMS ethers were regular for alditols and ω-deoxyalditols as one group, but internal-deoxyalditols (alditols having a methylene group within the chain) formed a separate group having consistently larger T R values for the same molecular weight. Sugars vs. deoxy sugars and lactones vs. deoxy lactones showed corresponding relationships.

A synthesis of methyl α-maltoside☆

Abstract A mixture of methanol, bromine, and silver carbonate readily converted ethyl 1-thio-β-maltoside into a mixture containing methyl α,β-maltoside and traces of maltose. The α-anomer, which initially formed 85% of the maltoside fraction, was enriched by selective oxidation of the β-anomer with chromic acid. Chromatographic purification gave a 65% yield of methyl α-maltoside of 97% anomeric purity. N.m.r. spectral data for methyl α-maltoside heptaacetate were obtained.