D- gluc ose D- gluc onic acid

1. Aldonic acids – acyclic derivatives of aldoses containing in their chain terminal position a carboxyl group instead of the carbonyl group. They can be obtained from any aldose by oxidation of its carbonyl group to carboxyl group. Their names are derived from the names of original aldoses by changing the suffix from -ose to -onic acid. D-glucoseD-gluconic acid

2. Aldonic acids Tollens reagent [Ag(NH3)2]+ D-glucose D-gluconic acid Br2, H2O pH 4-6 D-glucono-1,5-lactone D- glucono-1,4- lactone

3. Why lactones preferentially exist in 5-membered rings 25 °C 25 °C H2O H2O 91 % 9 % 27 % 73 % The reason Lactones, due to their resonance structures, contain two sp2atoms (carbon C-1 and oxygen ring atom), and thus, their pertinent four ring atoms are placed in a plane. Therefore the reason is that the five-membered rings much better suit such planar arrangements than the six-membered rings do.

4. Uronic acids (syn., glycuronic acids) – derivatives of aldoses containing in their chain terminal positions an aldehyde group and a carboxyl group. They can be derived from any aldose by changing its terminal hydroxymethyl group to carboxyl group. Similarly as aldoses, they normally exist in cyclic hemiacetal structures. Also similarly as aldonic acids, uronic acids simultaneously are also forming lactones and in aqueous solutions form with them equilibrium mixtures. According to the aldose, from which the uronic acid is derived, is also created its name; e. g., D-glucuronic acid is derived from D- glucose . Uronic acids abundantly occur as constituents of plant, animal and microbial polysaccharides. Methods of their preparation are based on the oxidation of the primary hydroxyl group of aldoses, reduction of monolactones of aldaric acids (similar method to the reduction of aldonic acid lactones to aldoses). D-glucose D-glucuronic acid D-glucurono-6,3-lactone

5. Aldaric acids – derivatives of aldoses, dicarboxylic acids formally derived from any aldose by oxidation of both terminal groups (aldehydic and primary alcoholic) to carboxylic groups. Their names are created from the names of original aldoses by changing their suffix –ose to –aric acid, e. g., D-glucaric acid from D-glucose. Because of the same functional groups at both ends of their carbon chains, similar rules are valid for their nomenclature as for alditols. Also total number of their stereoisomers is lower in comparison with that of aldoses. They can be prepared from aldoses or aldonic acids by oxidation with nitric acid, or from uronic acids by oxidation with bromine water. Similarly as aldonic acids or uronic acids, also aldaric acids form lactones, in some cases also dilactones (if stereochemical arrangement of their OH groups allows that). evaporation D-glucose D-glucaric acid D-glucaro-1,4:6,3-dilactone

6. Saccharinic acids- derivatives of monosaccharides with unbranched or branched chain, containing a carboxylic group and having a hydroxyl group substituted with hydrogen atom. Thus, they can be considered deoxyaldonic acid. There are three isomeric types; saccharinic acids, isosaccharinic acids and metasaccharinic acids. Saccharinic acids are built-up at a prolonged treatment of alkaline medium on monosaccharides (and reducing oligosaccharides) and are products of the benzil rearrangement of -dicarbonyl derivatives of sugars, which can be secondary products of the Lobry de Bruyn – Alberda van Ekenstein isomeization of aldoses or ketoses. Metasaccharinic acid (3-deoxyaldonic acid) Saccharin

7. Saccharinic acids build-up enediolate D-glucose(3-O-methyl-D-glucose) metasaccharinic acid benzilrearrangement Substitution of the -hydroxyl group to the carbonyl group of aldose or ketose favours the saccharinic acid build-up, preceeding via -elimination from the enediolate form and providing -dicarbonyl intermediate necessary for the benzil rearrangement.

8. Pyruvic acid N-Acetyl-D-mannosamine Neuraminic acid (Sialic) (Neu5Ac) T = tautomeizationA = aldolization = direction of the substituent orientation at cyclization Neuraminic acid is aldolization product of pyruvicacid and N-acetyl-D-mannosamine

9. Active ingredient of Relenza, the first drug for treatment of influenza based on the neuramidinase inhibition Neuraminic acid (Sialic acid) (Neu5Ac)

10. Neuraminic acid (Sialic acid) (Neu5Ac) Active ingredient of protichrípkového lieku Tamiflu, anotherdrug for treatment of influenza based on the neuramidinase inhibition

11. Reduction of aldoses to alditols i i i D-glucose D-glucitol (sorbitol) D-fructose D-mannitol i = NaBH4/pH 8 or NaHg/EtOH or H2/Ni/pressure

12. Methods of elongation of the carbon chain of aldoses (Ascent of series) • Kiliani-Fischer procedure - method of elongation of the carbon chain of aldoses. Base or acid catalyzed addition of cyanohydrin to an aldose aldózu provides a pair of epimeric nitriles of aldonic acids, which are converted by hydrolysis to one carbon elonged aldonic acids. These are converted by evaporation of aqueous solution to lactones, which are in mild acidic medium solution reduced with sodium amalgam or at low temperature with sodium borohydride to the correcponding aldoses.

13. Kiliani-Fischer procedure tautomerization 0 °C, pH 3 D-glucono-1,4-llactone D-glucofuranose D-glucopyranose

14. Methods of elongation of the carbon chain of aldoses (Ascent of series) • Sowden procedure - method of elongation of the carbon chain of aldoses. Base catalyzed addition of nitromethane to an aldose affords nitronic salts of an epimeric pair 1-deoxy-1-nitroalditols, which can be transformed to one carbon elonged aldoses by treatment with a strong acid (usually sulfuric acid, Nef reaction). • Two other modifications of the Sowden procedure, developed at the Institute of Chemistry, Slovak Academy of Sciences, Bratislava, are using either hydrogen peroxide/sodium molybdate treatment or ozone treatment of the nitronate salts, instead of their sulfuric acid treatment.

15. Sowden procedure Two other modifications of the Sowden procedure, developed at the Institute of Chemistry, Slovak Academy of Sciences, Bratislava, are using either hydrogen peroxide/sodium molybdate or ozone treatment, instead of sulfuric acid treatment of the nitronate salts.

16. Aldolization of sugars dihydroxyacetone qvantitatively D-fructose D-glyceraldehyde D-sorbose Major products Aldolizationof trioses is not reverse reaction, as resulting ketoses are stabilized by cyclization to their hemiketal tautomeric forms. D-psicose D-tagatose Minor products

17. Methods of contraction of the carbon chain of aldoses (Descent of series) • Wohl degradation - method of contraction of the carbon chain of aldoses. Starting aldose is by treatment with hydroxylamine transformed to aldose oxime, which by treatment with acetic anhydride and sodium acetate undergoes simultaneous acetylation and dehydration affording aldononitrile peracetate. Following treatment with Ag2O in aqueous ammonia causes its deacetylation and simultaneous elimination of cyanohydrin affording one carbon shorter aldose. There are several modifications of the procedure, especially for the last step simplifications, e.g., by treatment with sodium methoxide in methanol. • Substantially, this procedure is opposite to the Kiliani-Fischer procedure of elongation of the carbon chain of aldoses.

18. Wohl degradation

19. Reciprocity of the Kiliani-Fischer method of aldose carbon chain elongation and Wohlmethod of aldose carbon chain contraction

20. Methods of contraction of the carbon chain of aldoses (Descent of series) • Ruff degradation - method of contraction of the carbon chain of aldoses. Soluble (usually calcium) salts of aldonic acids by treatment with hydrogen peroxide in presence of ferric ions undergo oxidative decarboxylation and produce a one carbon shorter aldose. · · · Fe2+ + H2O2 Fe3+ + HO + HO- R = aldose moiety or aldonic acid moiety

21. Methods of contraction of the carbon chain of aldoses (Descent of series) • Weerman degradation - method of contraction of the carbon chain of aldoses. Aldonamide, derived from an aldonic acid, by treatment with alkaline hypochlorite or hypobromide undergoes the Hofmann degradation via isocaynate and decomposes to a one carbon shorter aldose. The new aldose, however, easily undergoes unwanted oxidation to aldonic acid at the conditions applied (with NaOBr or NaOCl). R = aldose moiety or aldonic acid moiety