Hassan S. El Khadem

Contribution of the reaction pathways involved in the isomerization of monosaccharides by alkali

Abstract The isomerization of eight hexoses and four pentoses, in aqueous KOH at pH 11.5 under nitrogen, was monitored by l.c. on cation (Pb 2+ )-exchange and reverse-phase columns. The primary epimerization reaction of pentoses and hexoses accounts for ∼90% of the saccharides found in solution after one week. The remaining saccharides were formed in part by fragmentation and recombination. This is indicated by the formation of hexoses (glucose and sorbose) during the isomerization of pentoses, and by the simultaneous formation of 3- and 4-epimeric hexuloses from hexoses. The aldol reaction responsible for the formation of hexoses (glucose, fructose, and sorbose) from glyceraldehyde at pH 11.5 was found to be fast ( t 1/2 = 2 h), which accounts for the rapid fragmentation and recombination observed.

Evidence of stable hydrogen-bonded ions during isomerization of hexoses in alkali

Abstract Epimeric pairs of aldohexoses and the related ketohexose were isomerized in aqueous KOH at various temperatures and pH values, and the mixtures then analyzed by h.p.l.c. on either a cation-exchange resin or a reversed-phase column. It was found that the proportions of starting aldohexoses remaining after several days often exceeded those of the same that were formed from the epimeric aldoses and the corresponding ketoses. The difference with allose, gulose, and mannose was much larger than with the other aldohexoses. These differences are rationalized by assuming that anomers having the OH groups attached to C-1, C-2, and C-3 in an axial—equatorial—axial or an equatorial—axial—equatorial arrangement form especially stable, hydrogen-bonded ions or molecular complexes that disturb the equilibrium state and affect the isomerization and mutarotation reactions.

Synthesis of nitrogen-bridged purine-like C-nucleosides from ethyl 2,5-anhydro-6-O-benzoyl-d-allonodithioate

Abstract Ethyl 2,5-anhydro-6- O -benzoyl- d -allonodithioate ( 1 ) was coupled with aminomethyl- and hydrazino-azines to afford the title compounds. Specifically, 1 was coupled with 2-(aminomethyl)pyridine to afford 3-β- d -ribofuranosylimidazolo-[1,5- a ]pyridine, with 2-hydrazinopyrazine to yield 3-β- d -ribofuranosyl-1,2,4-triazolo[4,3- a ]pyrazine, and with 2-hydrazinopyrimidine to form a 3-substituted 1,2,4-triazolo[4,3- a ]pyrimidine which underwent a Dimroth rearrangement to yield 2-β- d -ribofuranosyl-1,2,4-triazolo[1,5- a ]pyrimidine. Finally, compound 1 was coupled with 2-hydrazino-4-hydroxy-6-methylpyrimidine to yield 7-methyl-3-β- d -ribofuranosyl- 1,2,4-triazolo[4,3- a ]-5(8 H )-pyrimidone.

2-β-d-ribofuranosylbenzoxazole from 2,5-anhydro-d-allonoimidate, and 1,3-dimethyl-8-β-d-ribofuranosylxanthine from 2,5-anhydro-d-allono-thioimidates and -dithioates

Abstract The ability of imidates, thioimidates, and dithioates to react with o -aminophenol ( 2 ) and 5,6-diamino-1,3-dimethyluracil ( 6 ) was studied, using non-saccharide model compounds, as well as saccharide derivatives. All of the model compounds gave 2-methylbenzoxazole, but only ethyl dithioacetate gave a purine derivative with 6 . Methyl 2,5-anhydro- d -allonoimidate hydrochloride reacted with 2 to yield 2-β- d -ribofuranosylbenzoxazole, but failed to react with compound 6 . On reaction with compound 6 such fully acylated thioimidates as ethyl and benzyl 2,5-anhydrotri- O -benzoyl- or tri- O - p -toluoyl- d -allonothiomidate hydrochloride yielded amidines that underwent aromatization of the furanose ring. Such monoacylated thioimidates as ethyl or benzyl 2,5-anhydro-6- O -benzoyl-- d -allonothioimidate hydrochloride yielded, with compound 6 , 8-(5- O -benzoyl-β- d -ribofuranosyl)-1,3-dimethylxanthine, without aromatization. Such dithioates as benzyl 2,5-anhydro-6- O -benzoyl- d -allonodithioate and ethyl 2,5-anhydrotri- O -benzoyl- d -allonodithioate were obtained by treating the corresponding thioimidate with H 2 S in pyridine. With compound 6 , the first yielded 8-(5- O -benzoyl-β- d -ribofuranosyl)-1,3-dimethylxanthine, which afforded the free C -nucleoside 1,3-dimethyl-8-β- d -ribofuranosylxanthine on treatment with methanolic ammonia.

Hydrazine derivatives of carbohydrates and related compounds

Publisher Summary This chapter provides an overview of the hydrazine derivatives of carbohydrates and related compounds. Hydrazine, hydroxylamine, and hydrogen peroxide are highly reactive nucleophiles that add to carbonyl compounds to give N - and O -adducts, which are not usually isolated. The chapter presents an account of the rich chemistry of the hydrazine derivatives of sugars, the versatility of their structures, and their availability, which makes them valuable enantiomerically pure synthons for chiral products. For example, reduction of aldose hydrazones affords an important class of chiral amino- and iminodeoxy sugars that contain nitrogen in place of the oxygen present in the rings of natural sugars. These imino sugars exhibit a wide spectrum of biological activities, mainly attributable to their ability to act as enzyme inhibitors. Also of considerable interest are the carba-sugars—the carbocyclic analogs of monosaccharides—which are readily available from inosose phenylhydrazones. Members of both these classes of compounds—the carba-sugars and the imino sugars (“aza sugars”)—are capable of inhibiting enzymes because they mimic the enzymes natural substrates (the sugars). This chapter provides an overview of saccharide hydrazones and glycosylhydrazines and also discusses about saccharide osazones and poly(hydrazones).

The reaction of phenylhydrazine with squaric acid: a model for carbohydrate osazone formation

Abstract The reaction of squaric acid ( 1 ) with phenylhydrazine yields cyclobutanetetraone poly(phenylhydrazones) ( 2–4 ), as reported earlier, as well as squaric acid derivatives, reported here. The latter products are a salt, 1,3-dianilinocyclobutenediylium-2,4-diolate ( 5 ), and 1-anilino-2-phenylhydrazinocyclobutene-3,4-dione ( 6 ), which upon oxidation yields tautomeric forms of cyclobutanetetraone 1-anilide-2-phenylhydrazone ( 7a and 7b ). The structure of the compounds isolated was established by 1 H, 13 C, 2D COSY, and 2D J -resolved NMR spectroscopy. The similarity between the reaction of squaric acid ( 1 ) with phenylhydrazine and osazone formation can be seen from the analogy between compounds 2 , 6 , and 7b and intermediates produced during carbohydrate osazone formation, as well as from the fact that these compounds afford an osazone analog ( 4 ) when treated with phenylhydrazine. It was also found that compound 5 can be generated by a retro-osazone reaction when cyclobutanetetraone bis(phenylhydrazone) ( 2 ) is heated with aniline.

The mechanism of saccharide osotriazole formation

Abstract The first step in the proposed mechanism is the formation of an osazone–Cu(II) complex that undergoes a one-electron shift from the nitrogen of the ligand to the metal in the complex which is reduced to Cu(I). This complex decomposes with the liberation of Cu(I) + , a ligand radical which undergoes a set of one-electron shifts to form a phenylimine radical (Ph–NH) and the triazole. The Cu(I) + produced is converted to Cu(II) 2+ and Cu 0 by disproportionation.

Oxidation of Monosaccharides with Oxygen in Alkaline Solution. Separation, Identification and Estimation of the Aldonic Acids Produced by Liquid Chromatography1,2

Abstract A reliable liquid chromatographic method has been developed for the separation, identification and estimation of the products formed when saccharides are oxidized in alkaline solution with oxygen. The technique was then used to quantitatite the acids produced when glucose is subjected to such an oxidation. The Bio-Rad cationg exchange column HPX-87H+, when eluted with 0.01 N H2SO4 and attached to a UV detector, was found to be satisfactory. Quanitative estimation of the products formed during the oxidation of glucose was achieved by withdrawing aliquots from the reaction mixture and injecting them directly into the chromatographic system. It was found that about 90% of the oxidation products formed were produced via a 1,2-enediol and less than 10% via a 2,3-enediol. The results confirmed the mechanism proposed by Isbell to account for the acids produced.

Resonance-stabilized phenylazo-ene-phenylimine cations of cyclobutanetetraone derivatives.

Cyclobutenedione phenylazo-phenylamines were found to exhibit bathochromic shifts in acidic media and hypsochromic shifts in basic media, like phenylazo-phenylhydrazones. The bathochromic shifts are due to the formation of resonance-stabilized cations and the hypsochromic shifts to enolization. The phenylazo-phenylamines and their cations and anions have been studied by NMR spectroscopy.

The cations and anions of cyclobutanetetraone poly(phenylhydrazones)

Six cyclobutanetetraone poly(arylhydrazones) have been treated with acids and bases, and the structures of the resulting anions and cations studied by UV-Vis absorption and NMR spectroscopy. In acid media, all the hydrazones studied formed cations, which exhibited bathochromic shifts due to the extension of their resonance systems. However, in bases, only some (those which could enolize) formed anions that exhibited hypsochromic shifts; the others were unaltered.