1 Carbohydrates Sugars or Saccharides One of the most abundant compounds of living cells In living cells (plants) -> carbohydrates are made by photosynthesis - Monosaccharides : C 3 -C 9 - Oligosaccharides : 2-10 units

2 Carbohydrates Monosaccharides (biological sugars –ose) Most frequently found in nature: - hexoses (six-carbon sugars) -> glucose and fructose - pentoses (five-carbon sugars) -> ribose S, R Configuration 2 Enantiomers Fischer Projection Highest Oxidation state

3 Carbohydrates Monosaccharides (biological sugars –ose) Most frequently found in nature: - hexoses (six-carbon sugars) -> glucose and fructose - pentoses (five-carbon sugars) -> ribose Aldoses Ketoses PyranosideFuranoside

4 Carbohydrates Monosaccharides D-Aldoses in the range of C3-C6

5 Carbohydrates Monosaccharides D-Ketoses in the range of C3-C6

6 Carbohydrates Monosaccharides Stereochemistry D-Erythrose + L-Erythrose -> Enantiomers D-Erythrose + D-Threose -> Diastereoisomers D-Erythrose + L-Threose -> Diastereoisomers D-glucose + L-glucose -> Enantiomers

7 Carbohydrates Monosaccharides Enolization and Isomerization I somerization Epimerization Base-catalysed in water: -> Epimerization + isomerization

8 Carbohydrates Monosaccharides Cyclic hemiacetals + hemiketals

9 Carbohydrates Monosaccharides Cyclic hemiacetals + hemiketals -> glucose

10 Carbohydrates Monosaccharides Cyclic hemiacetals + hemiketals -> glucose DL  α-Sugars have the -CH 2 OH group and the anomeric hydroxyl group trans. β-Sugars have the -CH 2 OH group and the anomeric hydroxyl group cis.

11 Carbohydrates Monosaccharides Cyclic hemiacetals + hemiketals -> glucose Glucopyranoside more stable -> almost 100% in pyranoside form

12 Carbohydrates Monosaccharides Cyclic hemiacetals + hemiketals -> ribose In solution mainly in pyranoside form (76%) In nucleotides (or other combinations) mostly found in furanose form

13 Carbohydrates Monosaccharides Cyclic hemiacetals + hemiketals -> fructose

14 Carbohydrates Monosaccharides Cyclic hemiacetals + hemiketals -> fructose In solution mainly in pyranoside form (67%) In combinations mostly found in furanose form

15 Carbohydrates Monosaccharides The anomeric center Carbonyl group is planar -> attack of OH from either side possible -> 2 epimeric structures (anomers) Both anomers are in equillibrium in solution Epimer (Anomer) Epimers: α -> anomeric center + highest chiral center -> different configuration (R,S convention) Hydroxyl (OH) on anomeric C Down -> α-D-sugars and β-L- sugars β -> anomeric center + highest chiral center -> same configuration (R,S convention) Up -> β-D-sugars and α-L-sugars

16 Carbohydrates Monosaccharides The anomeric center Carbonyl group is planar -> attack of OH from either side possible -> 2 epimeric structures (anomers) Both anomers are in equillibrium in solution Epimers: β -> anomeric center + highest chiral center -> same configuration (R,S convention) α -> anomeric center + highest chiral center -> different configuration R,R-> β S,R-> α

17 Carbohydrates Monosaccharides The anomeric center Carbonyl group is planar -> attack of OH from either side possible -> 2 epimeric structures (anomers) In solution -> all 4 forms in equillibrium !!! Aldohexoses Ketose

18 Carbohydrates Monosaccharides The anomeric center Esterfication -> freezes sugar in its anomeric form (no interconvertion between α and β any more)

19 Carbohydrates Monosaccharides Alditols Reduction of sugars -> reducing agent (NaBH 4 ) -> reduces aldehydes + ketons Reduction occurs at small amount of open chain form -> shift in equilibrium -> total reduction achieved Reduction of Aldoses -> 1 product (primary alcohol) -> Alditols Reduction of Ketoses -> 2 products (secondary alcohol) -> Alditols

20 Carbohydrates Monosaccharides Glycosides (replace suffix –ose with –oside) -> Reaction at C1 (anomeric C) Hemiacetals + Alcohol -> Acetals (Glycoside) Hemiketals + Alcohols -> Ketals (Glycoside) OH on the anomeric C1

21 Carbohydrates Monosaccharides Glycosides (replace suffix –ose with –oside) Hemiacetals + Alcohol -> Acetals (Glycoside) Hemiketals + Alcohols -> Ketals (Glycoside)

22 Carbohydrates Monosaccharides Glycosides (replace suffix –ose with –oside) -> Reaction at C1 Hemiacetal/Hemiketal + Alcohol -> O- Glycoside -> Polysaccharides Hemiketal/Hemiketal + Amine -> N-Glycoside

23 Carbohydrates Monosaccharides Glycosides (replace suffix –ose with –oside) Hemiacetal/Hemiketal + Alcohol -> O- Glycoside -> Polysaccharides Hemiketal/Hemiketal + Amine -> N-Glycoside Template for aspirin Nucleotides of RNA and DNA

24 Carbohydrates Monosaccharides Glycosides (replace suffix –ose with –oside) Glucose + MeOH -> Acetal --  reaction works directly Glucose + complex alcohol -> not that easy Example: Production of salicin -> Template for Aspirin

25 Carbohydrates Monosaccharides Glycosides (replace suffix –ose with –oside) Glucose + MeOH -> Acetal --  reaction works directly Glucose + complex alcohol -> not that easy Example: Production of salicin -> Template for Aspirin

26 Carbohydrates Monosaccharides Cyclic Acetals + Ketals -> protecting groups 2 OH groups are cis conformation -> reaction with keton C6

27 Carbohydrates Monosaccharides Modified sugars -> in cell membranes

28 Carbohydrates Oligosaccharides -> a few monomers Found in dietary products

29 Carbohydrates Polysaccharides In Plant cell wall -> cotton In animal and plant cells

30 Carbohydrates Polysaccharides Glycogen -> mammalian sugar storage

31 Carbohydrates Polysaccharides Starch: amylose + amylopectine -> main plant food reserve

32 Carbohydrates Polysaccharides - Hydrolysis 1.Chemically: - under harsh conditions: with hot acid -> monosaccharides (glucose) - under mild conditions: with acid -> oligosaccharides (randomly) 2. Enzymatic: very specific hydrolysis -> α-amylase -> hydrolysis α 1 -> 4 bonds in starch (mainly maltose + glucose) -> α-1,6-glucosidase -> hydrolysis α 1 -> 6 bonds in starch -> lactase -> hydrolysis lactose (high activity of enzyme in infants – low activity in adults -> intolerance) -> cellulase -> hydrolysis β 1 -> 4 bonds -> animals do not have it (need bacteria)

33 Carbohydrates Oxidation of sugars Under mild conditions -> with cupric ion (Fehling’s solution) or Br 2 -> oxidation of aldehyde group -> acid (aldonic acid) If sugars are glycosidic linked (acetal formation) -> aldehyde group not available for oxidation -> no reducing sugars If sugar are free -> reducing sugars

34 Carbohydrates Oxidation of sugars Under strong conditions -> with HNO 3 -> oxidation of aldehyde group + alcohol groups (primary alcohol) -> diacid (aldaric acid)

35 Carbohydrates Oxidation of sugars Determination of glucose level in blood or urine -> oxidation of glucose –> H 2 O 2 involved in second reaction -> colorimetric or voltametric sensor (Biosensor) Diabetes mellitus: Insulin deficiency Insulin regulates blood sugar (glucose) level If glucose level is high -> insulin level increases -> prevents break down of glycogen into glucose and conversion of fat or protein into glucose -> blood glucose level will sink again If glucose level is low -> insulin level drops -> more glucose produced -> blood glucose level will rise

36 Carbohydrates Oxidation of sugars Terminal OH group oxidized in Aldoses -> Uronic acids Pectins: in cell walls of fruits -> acid solutions form gels -> jam making Also oxidized by most enzymes

37 Carbohydrates Oxidation of sugars Terminal OH group oxidized in Aldoses -> Uronic acids Pain relieferEven stronger pain reliefer Morphine metabolism in human body -> make it more soluble -> excretion

38 Carbohydrates Oxidation of sugars Vitamin C: most animals can synthesize Vitamin C – Humans and primates cannot NOT -> synthesized in liver from glucose Essential for: - formation of structural proteins in skin, bones, ligaments - cofactor in synthesis reactions of amino acids and modifications - antioxidants Deficiently (scurvy) -> muscular pain, skin lesions, fragile blood vessel, bleeding gums, tooth loss

39 Carbohydrates Aminosugars Replacement of one OH group by a amino group In nature -> done by enzymes -> 2-amino-2-deoxy sugars Chitin: insect skeleton and shells of crustaceans

40 Carbohydrates Aminosugars Replacement of one OH group by a amino group In nature -> done by enzymes -> 2-amino-2-deoxy sugars Bacterial cell walls -> glycycosidic bond cleaved by lysozyme Lysozyme β-lactam antibiotics -> inhibit peptidase linking peptide bond during biosythesis of cell wall

41 Carbohydrates Aminosugars Replacement of one OH group by a amino group In nature -> done by enzymes -> 2-amino-2-deoxy sugars Blood groups: Determined by glycoproteins