Carbohydrates Hydrates of Carbon: General Formula Cn(H2O)N Plants
Chapter 25: Carbohydrates
hydrates of carbon: general formula Cn(H2O)n
Plants: photosynthesis hν 6 CO2 + H2O C6H12O6 + 6 O2
Polymers: large molecules made up of repeating smaller units (monomer)
Biopolymers: Monomer units: carbohydrates (chapter 25) monosaccharides peptides and proteins (chapter 26) amino acids nucleic acids (chapter 28) nucleotides
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25.1 Classification of Carbohydrates: I. Number of carbohydrate units monosaccharides: one carbohydrate unit (simple carbohydrates) disaccharides: two carbohydrate units (complex carbohydrates) trisaccharides: three carbohydrate units polysaccharides: many carbohydrate units CHO H OH HO HO HO H HO HO O HO O glucose H OH HO HO OH HO H OH OH
CH2OH HO HO HO O HO O HO HO O HO HO O HO HO HO O O O O O HO HO O HO HO HO O O HO HO HO galactose OH + glucose O glucose = lactose polymer = amylose or cellulose 316
160 II. Position of carbonyl group at C1, carbonyl is an aldehyde: aldose at any other carbon, carbonyl is a ketone: ketose
III. Number of carbons three carbons: triose six carbons: hexose four carbons: tetrose seven carbons: heptose five carbons: pentose etc.
IV. Cyclic form (chapter 25.5)
CHO CHO CHO CHO CH2OH H OH HO H H OH H OH O
CH2OH H OH H OH HO H HO H CH2OH H OH H OH H OH
CH2OH H OH H OH CH OH 2 CH2OH glyceraldehyde threose ribose glucose fructose (triose) (tetrose) (pentose) (hexose) (hexose) 317 (aldohexose) (ketohexose)
25.2: Depicting carbohydrates stereochemistry: Fischer Projections: representation of a three-dimensional molecule as a flat structure. Tetrahedral carbon represented by two crossed lines:
horizontal line is coming vertical line is going back out of the plane of the behind the plane of the page (toward you) paper (away from you) substituent carbon (R)-glyceraldehyde
CHO CHO CHO H OH H OH H C CH2OH HO CH2OH CH2OH
(S)-glyceraldehyde
CHO CHO CHO HO H HO H HO C CH OH H 2 CH OH CH2OH 2 318
161 Manipulation of Fischer Projections 1. Fischer projections can be rotate by 180° only!
CHO CH2OH CHO CH2OH 180 ° H OH HO H 180 ° HO H H OH
CH2OH CHO CH2OH CHO (R) (R) (S) (S)
180° 180°
Valid Valid Fischer Fischer projection projection
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a 90° rotation inverts the stereochemistry and is illegal!
90 ° CHO OH H OH ! OHC CH2OH
CH2OH H (R) (S)
90 °
This is not the correct convention 90° for Fischer projections
Should be projecting toward you Should be projecting away you
This is the correct convention for Fischer projections and is the enantiomer
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162 2. If one group of a Fischer projection is held steady, the other three groups can be rotated clockwise or counterclockwise. hold steady CHO CHO
H OH HO CH2OH
CH2OH H (R) (R)
CHO H HO H OHC OH hold steady CH2OH CH2OH (S) (S)
120° 120°
hold hold steady steady hold steady
120° 120°
hold hold 321 hold steady steady steady
Assigning R and S Configuration to Fischer Projections 1. Assign priorities to the four substitutents according to the Cahn-Ingold-Prelog rules 2. Perform the two allowed manipulations of the Fischer projection to place the lowest priority group at the top (or bottom). 3. If the priority of the groups 1-2-3 are clockwise then assign the center as R, if 1-2-3 are counterclockwise then assign the center as S.
2 place at the top 4 CO2H H 1 H2N H 4 2 HO2C NH2 1 hold steady CH3 CH3 rotate other 3 3 three groups counterclockwise 1-2-3 counterclockwise = S
2 4 2 CO2H H CO2H 4 1 2 H NH2 1 H2N CO2H H2N CH3 CH3 1 3 CH3 H 3 3 4 1-2-3 clockwise = R 322
163 Fischer projections with more than one chiral center:
1 CHO CHO 2 HO H HO H 3 H OH H OH
4 CH2OH CH2OH Threose 2 CHO H 4 1 2 1 2 4 2 HO H OHC S OH 3 3 4 H OH 4 H OH 1 Hold Steady 1 3 CH2OH CH2OH 3 (2S, 3R)
H 4 H 4 Hold Steady 2 1 2 1 2 S 2 OHC OH OHC OH 3 3 HO CH OH 4 H OH 1 1 2 R 3 H CH OH 2 4 3 323
25.3 D, L Sugars Glyceraldhyde- before the R/S convention, stereochemistry was related to (+)-glyceraldhyde CHO CHO H OH HO H
CH2OH CH2OH D-glyceraldehyde L=glyceraldehyde R-(+)-glyceraldhyde (+)-rotation = dextrorotatory = D
D-carbohydrate have the -OH group of the highest numbered chiral carbon pointing to the right in the Fisher projection as in R-(+)-glyceraldhyde
CHO CHO CHO CHO H OH H OH HO H HO H HO H H OH HO H H OH H OH H OH HO H HO H
H OH CH2OH CH2OH HO H
CH2OH CH2OH
D- glucose D-ribose L-ribose L- glucose
Most carbohydrate in nature are of the D-series 324
164 For carbohydrates, the convention is to put the carbonyl group at the top for aldoses and closest to the top for ketoses. The carbons are numbered from top to bottom.
Carbohydrates are designated as D- or L- according to the stereochemistry of the highest numbered chiral carbon of the Fischer projection. If the hydroxyl group is pointing to the right in the Fischer projection, the sugar is designated as D (Dextro: Latin for on the right side). If the hydroxyl group is pointing to the left in the Fischer projection, the sugar is designated as L (Levo: Latin for on the left side). Most naturally occurring carbohydrates are of the D-configuration.
1 CHO 1 H 2 OH CHO 3 2 HO H H OH 3 4 HO H H OH highest numbered highest numbered 5 HO 4 H stereogenic carbon H OH stereogenic carbon 5 CH2OH 6 CH2OH 325 D-Glucose L-Arabinose
24.4 Configuration of the Aldoses: triose tetroses CHO CHO CHO H OH HO H H OH H OH H OH CH2OH CH2OH CH2OH D-glyceraldehyde D-erythrose D-threose
CHO CHO CHO CHO H OH HO H H OH HO H H OH H OH HO H HO H H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH
D-ribose D-arabinose D-xylose D-lyxose
CHO CHO CHO CHO CHO CHO CHO CHO H OH HO H H OH HO H H OH HO H H OH HO H H OH H OH HO H HO H H OH H OH HO H HO H H OH H OH H OH H OH HO H HO H HO H HO H H OH H OH H OH H OH H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH
D-allose D-altrose D- glucose D-mannose D-gulose D-idose D-galactose D-talose 326
165 25.5 Cyclic structures of Monosaccharides: hemiacetal formation
O H+ HO OR2 + R2OH R1 H R1 H
hemiacetal
O OH H H cyclic hemiacetal OH O
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166 25.6: Monosaccharide anomers: mutarotation Anomers: the hemiacetal or hemiketal carbon (the carbonyl carbon of the open form) is a new chiral center and is referred to as the anomeric carbon (hemi-acetal carbon of the closed form)
CH OH Trans 2 CH2OH Cis HO HO O O HO HO H OH HO HO OH H
α-D-Glucopyranose (36%) β-D-Glucopyranose (64%) (α-anomer: C1-OH and (β-anomer: C1-OH and CH OH are cis) CH2OH are trans) 2
The hemiacetal forms of pyranoses adopts a chair conformation. The hydroxyl of the new anomeric (acetal)carbon can be axial (α) or equatorial ( ). The anomers are diastereomers. β 329
The α- and β-anomers are in equilibrium. They interconvert through the open form. The pure anomers can be isolated by crystallization. When the pure anomers are dissolved in water they undergo mutarotation, the process by which they return to an equilibrium mixture of the anomers
HO HO OH HO HO O O HO HO OH HO HO H CHO H H OH HO H β-anomer H OH H OH CH OH 2 HO HO OH HO HO O HO H HO H HO HO O OH α-anomer 330
167 25.7: Reactions of monosaccharides
reacts like a carbonyl CHO H OH HO HO H HO reacts like HO O reacts like alcohols alcohols H OH HO H OH OH
CH2OH Ester formation: H3C O O O O HO H C O CH O HO 3 3 H3C O O HO OH O O HO O CH3 pyridine H3C O O O !-D-glucopyranose O CH3 Ether Formation
HO Ag O, CH I H3CO HO 2 3 O H3CO HO OH H CO O HO 3 OCH3 H3CO
!-D-glucopyranose 331
Glycoside Formation
HO OR + R O OR O H+ 2 H 2 2 + R2OH R1 H R1 H R1 H R2OH hemiacetal acetal
O OH OR2 H H+ H H O O OH R2OH
cyclic hemiacetal glycoside
OH OH CH OH, HCl OH HO 3 O HO HO O + HO OH HO HO O HO OCH3 HO HO OCH3 methyl !-D-glucopyranoside methyl "-D-glucopyranoside
When R2OH is another carbohydrate unit, complex carbohydrate are formed. 332
168 The Koenigs-Knorr Reaction
AcO AcO AcO HBr ROH, Ag O AcO 2 O AcO AcO O AcO OAc O AcO AcO AcO OR AcO AcO Br
Neighboring group participation directs the stereochemistry of the glycosidation reaction 333
Reduction of Monosaccharides
reacts like a carbonyl CHO CH2OH H OH HO H OH HO HO H NaBH4 HO O HO H H OH HO H OH H OH OH H OH CH2OH CH2OH alditol Oxidation of Monosaccharides: aldoses can be oxidized to
aldonic acids with Ag(I) in NH3 (Tollin’s reagent), Cu(II) (Fehling’s or Benedict’s reagent) or Br2.
CHO CO2H H OH Ag(I) Ag(0) H OH HO H HO H H OH H OH NH3 H OH H OH
CH2OH CH2OH aldonic acid
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169 Reducing sugars: carbohydrates that can be oxidized to aldonic acids.
2-ketose
Oxidation to aldaric acids:
CHO CO2H H OH H OH HO H HNO3, heat HO H H OH H OH H OH H OH
CH2OH CO2OH aldaric acid 335
Killiani-Fischer Synthesis- chain lengthening of monosaccharides
N NH O H H C C C
HO H HO H + HO H HCN H2, Pd H3O HO H HO H HO H H OH H OH H OH H OH H OH H OH CH OH CH OH CH OH CHO 2 2 2 HO H D-Glucose H OH H OH
CH2OH N NH O D-Arabinose C H C H C H OH H OH H OH HO H H , Pd + HCN 2 HO H H3O HO H H OH H OH H OH H OH H OH H OH CH OH 2 CH2OH CH2OH D-Mannose
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170 The Wohl Degradation: chain shortening of monosaccharides
HON H N CHO C C H OH H OH H OH CHO (CH3CO)2O CH3ONa HO H H2NOH HO H HO H HO H HO H CH CO Na - HCN HO H 3 2 HO H HO H H OH H OH - H2O H OH H OH CH2OH CH OH CH OH 2 CH2OH 2
D-galactose oxime cyanohydrin D-Lyxose
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25.8 Stereochemistry of Glucose: The Fischer Proof (. . . as applied to the D-tetroses and D-pentoses)
1) KCN CHO CO2H 2) H , Pd HNO , 2 H OH 3 H OH 3) H2O heat H OH H OH
CH2OH CO2H
D-(-)-erythrose tartaric acid
CHO H OH Killiani-Fischer synthesis CH2OH D-(+)-glyceraldehyde
CHO CO2H HNO3, HO H heat HO H H OH H OH 1) KCN CH2OH CO2H 2) H2, Pd 3) H2O D-(-)-threose D-(-)-tartaric acid
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171 1) KCN CHO CO2H 2) H2, Pd 3) H O H OH HNO3, H OH 2 heat H OH H OH H OH H OH CH OH 2 CO2H D-(-)-ribose ribonic acid CHO H OH Killiani-Fischer H OH synthesis
CH2OH D-(-)-erythrose
CHO CO2H HO H HNO3, HO H heat H OH H OH 1) KCN H OH H OH 2) H2, Pd CH OH 3) H2O 2 CO2H D-(-)-arabinose arabonic acid
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1) KCN CHO CO2H 2) H , Pd 2 H OH HNO3, H OH 3) H2O heat HO H HO H H OH H OH
CH2OH CO2H D-(+)-xylose xylonic acid CHO HO H Killiani-Fischer H OH synthesis
CH2OH D-(-)-threose
CHO CO2H HNO3, HO H HO H heat HO H HO H 1) KCN H OH H OH 2) H2, Pd CH OH CO2H 3) H2O 2 D-(-)-lyxose lyxonic acid
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172 CHO CHO CHO CHO H OH HO H H OH HO H H OH H OH HO H HO H H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH D-ribose D-arabinose D-xylose D-lyxose
CHO CHO CHO CHO CHO CHO CHO CHO H OH HO H H OH HO H H OH HO H H OH HO H H OH H OH HO H HO H H OH H OH HO H HO H H OH H OH H OH H OH HO H HO H HO H HO H H OH H OH H OH H OH H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH D-allose D-altrose D- glucose D-mannose D-gulose D-idose D-galactose D-talose
CO2H CO2H CO2H CO2H CO2H CO2H CO2H CO2H H OH HO H H OH HO H H OH HO H H OH HO H H OH H OH HO H HO H H OH H OH HO H HO H H OH H OH H OH H OH HO H HO H HO H HO H H OH H OH H OH H OH H OH H OH H OH H OH
CO2H CO2H CO2H CO2H CO2H CO2H CO2H CO2H
optically optically optically optically optically optically optically optically inactive active active active active active inactive active
enantiomers 341
25.9: Disaccharides OH OH OH ROH HO HO HO -or- HO O HO O HO O OH OR HO HO HO OR When ROH is another carbohydrate unit, a disaccharide formed.
HO HO HO O HO 1 HO 4' maltose HO O O (1,4'-!-glycoside) HO HO HO O HO HO + HO O OH HO HO OH HO OH HO HO glucose glucose HO O 4' cellobiose HO O HO O (1,4'-"-glycoside) 1 HO HO OH
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173 HO HO HO HO HO HO HO HO O HO O HO O HO Ag(I) HO O O OH O OH + Ag(0) O HO HO HO HO HO H [O] HO OH HO HO HO OH O O reducing end cellobiose and maltose are reducing sugar
HO HO HO HO Ag(I) HO HO HO HO HO + Ag(0) O 4' O [O] HO HO HO O O O O OH O OH HO HO HO HO 1 HO H HO OH HO HO HO lactose OH O O (1,4'- -glycoside) reducing ! end lactose is a reducing sugar
HO HO Ag(I) HO O HO No reaction HO 1 ! [O] 2' glucose O " O sucrose is not OH fructose sucrose HO a reducing sugar (1,2'-glycoside) No reducing end 343 OH
25.10 Polysaccharides and the their synthesis (please read) Cellulose: glucose polymer made up of 1,4’-β-glycoside linkages HO HO HO HO HO HO O O O O O O O O O O O O O HO HO HO HO HO HO HO HO HO HO HO HO H H H H H H
Amylose: glucose polymer made up of 1,4’-α-glycoside linkages HO HO H HO HO HO O O H H HO O O H H O O H O O O HO HO HO HO O O HO HO HO HO HO O O HO HO HO
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174 Amylopectin and glycogen: branched amylose related
glucose polymers HO O O HO H HO HO O O HO H HO HO HO H HO O HO O O H H HO O O H H O O H O O O HO HO HO HO O O HO HO HO HO HO O O HO HO HO 25.11 Other Important Carbohydrates Deoxy sugars: carbohydrates that are missing a hydroxyl group
ribose C H O 2-deoxyribose CHO HO H OH HO HO O O H H H OH OH HO O O H OH OH HO OH H OH OH HO H OH OH OH OH CH2OH OH CH2OH ribopyranose ribofuranose 2-deoxyribopyranose 2-deoxyribofuranose found in found in 2’-deoxyribonucleic ribonucleic acid (RNA) acid (DNA) 345
Eight essential monosaccahrides
OH HO HO HO HO OH CH HO HO 3 O O HO O O HO O HO HO HO HO HO HO HO HO OH OH OH OH OH CHO HO H CHO CHO CHO H OH H OH H OH HO H CHO H OH HO H HO H HO H H OH HO H HO H H OH H OH HO H H OH H OH CH3 H OH H OH
CH2OH CH2OH CH2OH CH2OH L-fucose D-galactose D- glucose D-mannose D-xylose (6-deoxy-L-galactose HO2C
OH O HO OH HO HO HO O HO O HN OH HO OH HN HN OH OH OH O CO2H O O O H H CHO CHO H OH H NHCOCH H NHCOCH 3 3 H3COCHN H HO H HO H HO H H OH HO H H OH H OH H OH H OH CH OH CH OH 2 2 CH2OH 346 N-acetylglucosamine N-acetylgalactosamine N-acetyl-D-neuraminic acid
175 25.12 Cell-Surface Carbohydrates and Carbohydrate Vaccines (please read): glycobiology Glycoproteins: glycosides of proteins
HO HO O HO X Protein HO X= -O- or -NH-
O CH3 O carbohydrate carbohydrate O N O N H H HN HN
serine threoine
O H N carbohydrate N H O HN asparagine
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