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Home , Aldonic acid, Allose, Altrose, Furanose, Glyceraldehyde, Gulose

Chapter 23:

hydrates of : general formula Cn(H2O)n

Plants: hν 6 CO2 + 6 H2O C6H12O6 + 6 O2

Polymers: large molecules made up of repeating smaller units (monomer)

Biopolymers: Monomer units: carbohydrates (Chapter 23) peptides and proteins (Chapter 25) amino acids nucleic acids (Chapter 26) nucleotides

Synthetic Polymers (Chapter 27) various

261

23.1: Classification of Carbohydrates. I. Number of units monosaccharides: one carbohydrate unit (simple carbohydrates) : two carbohydrate units (complex carbohydrates) : three carbohydrate units (): many carbohydrate units

CHO H OH HO HO HO H HO HO O HO O 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 OH O 262 glucose glucose

118 II. Position of the carbonyl at C1 is an : the carbonyl at any other carbon is a :

III. Number of three carbons: six carbons: four carbons: seven carbons: five carbons: etc.

IV. Cyclic form (Chapter 23.6 and 23.7)

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 glucose (pentose) (triose) (tetrose) (hexose) (hexose) (aldohexose) (ketohexose) 263

23.2: Fischer Projections and the D, L Notation. Representation of a three-dimensional molecule as a flat structure (Ch. 7.7). 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 CH OH HO CH2OH 2

(S)-(-)-glyceraldehyde

CHO CHO CHO HO H HO H HO C CH2OH H CH2OH CH2OH

264

119 before the R/S convention, stereochemistry was related to (+)-glyceraldehyde

CHO CHO H OH HO H

CH2OH CH2OH

D-glyceraldehyde L-glyceraldehyde R-(+)-glyceraldehyde S-(-)-glyceraldehyde (+)-rotation = dextrorotatory = d (-)-rotation = levorotatory = l

D-carbohydrates have the -OH group of the highest numbered chiral carbon pointing to the right in the as in R-(+)-glyceraldehyde.

For carbohydrates, the convention is to arrange the Fischer projection with the carbonyl group at the top for and closest to the top for . The carbons are numbered from top to bottom.

265

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 of the highest numbered chiral carbon is pointing to the right, the carbohydrate is designated as D (Dextro: Latin for on the right side). If the hydroxyl group is pointing to the left, the carbohydrate 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 H 4 OH HO H highest numbered highest numbered 5 HO 4 H "chiral" carbon H OH "chiral" carbon 5 CH2OH 6 CH2OH

D-Glucose L-

CHO HO H CHO H OH HO H HO H H OH highest numbered highest numbered H OH "chiral" carbon HO H "chiral" carbon CH2OH CH2OH 266 L- glucose D-Arabinose

120 23.3: The Aldotetroses. Glyceraldehyde is the simplest carbohydrate (C3, aldotriose, 2,3-dihydroxypropanal). The next carbohydrate are aldotetroses (C4, 2,3,4-trihydroxybutanal).

aldotriose

CHO CHO H OH HO H

CH2OH CH2OH

D-glyceraldehyde L-glyceraldehyde

aldotetroses 1CHO 1 CHO 2 HO 2 H highest numbered H OH highest numbered 3 3 "chiral" carbon H OH HO H "chiral" carbon 4 4 CH2OH CH2OH D- L-erythrose

CHO CHO HO H H OH highest numbered highest numbered HO H "chiral" carbon H OH "chiral" carbon CH2OH CH2OH D-threose L-threose 267

23.4: Aldopentoses and Aldohexoses.

Aldopentoses: C5, three chiral carbons, eight stereoisomers

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- D-

Aldohexoses: C6, four chiral carbons, sixteen stereoisomers

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- D- D- glucose D- D- D- D-galactose D-

268

121 Manipulation of Fischer Projections 1. Fischer projections can be rotate by 180° (in the plane of the page) 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

269

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

270

122 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 hold 271 steady steady steady

Assigning R and S Configuration to Fischer Projections 1. Assign priorities to the four substituents 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 other groups 1→2→3 is clockwise then assign the carbon as R, if the priority of the other groups 1→2→3 is 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 272

123 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

273

23.5: A Mnemonic for Carbohydrate Configuration. (please read)

25.6: Cyclic Forms of Carbohydrates: Forms.

O H+ + HO OR2 H , R2OH R2O OR2 + R2OH R1 H (Ch. 17.8) R1 H R1 H

acetal

O OH OR

H + H H H , ROH

OH O Ch. 23.1425.13 O

cyclic hemiacetal mixed acetal ()

274

124 Cyclization of carbohydrates to the hemiacetal creates a new chiral center. The hemiacetal or hemiketal carbon of the cyclic form of carbohydrates is the anomeric carbon. Carbohydrate that differ only in the stereochemistry of the anomeric carbon are called and designated as α and β.

CHO * H OH H H O O H OH H H * + H H * H OH H H H OH CH2OH OH OH OH OH D-erythrose

Converting Fischer Projections to Haworth formulas

275

23.7: Cyclic Forms of Carbohydrates: Forms. H H 5 OH 5 H O H O OH H H 4 4 1 H H 1 H H 1 CHO HO HO H 2 2 H 3 H OH 3 3 HO OH OH OH H OH H H H H 1 new chiral 4 5 4 3 2 H OH HO CHO H center 5 H 5 H H H OH OH OH OH 5 H H O H OH H H H 4 H H 1 4 H H 1 D-ribose HO HO 2 OH 3 2 O 3 HO OH OH OH ribopyranose

6 CH OH 2 6 CH OH 5 2 OH 5 H O H O OH H H 4 4 1 1 OH H 1 OH H CHO HO HO H 2 3 2 H 3 H OH 6 H OH 3 H OH HO H HOH C H OH H 2 1 new chiral 5 2 H 4 OH HO 4 3 CHO center 6 CH2OH 6 5 CH2OH 5 HOH2C H H OH H OH OH 5 6 H H O H OH H H H 4 OH H 1 4 OH H 1 D-glucose HO HO 2 OH 3 2 O 3 H OH H OH glucopyranose 276 Note: the pyranose forms of carbohydrates adopt chair conformations.

125 23.8: . The α- and β-anomers are in equilibrium, and 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 .

HOH C 2 HOH C cis OH 2 HO HO O O HO HO OH HO HO CHO H H OH H β-D-Glucopyranose (64%) HO H [ ] +18.7° H OH (β-anomer: C1-OH and α D H OH CH2OH are cis) CH2OH HOH C 2 HOH C OH 2 trans HO HO O HO H HO H HO HO O OH

α-D-Glucopyranose (36%) [α]D +112.2° ( -anomer: C1-OH and α 277 acid-catalyzed mechanism: p. 959 CH2OH are trans)

23.9: Carbohydrate Conformation: The (please read) 23.10: Ketoses. Ketoses are less common than aldoses

CH2OH CH2OH CH OH 2 CH2OH O O O O CH2OH HO H H OH H OH O HO H H OH H OH HO H H OH CH2OH H OH CH2OH CH OH 2 H OH H OH CH2OH CH2OH D- Dxylulose D-fructose D-sedohepuloase Fructofuranose and Fructopyranose

1 6 CH2OH 6 6 CH OH OH 2 HOH C H OH HOH C O 2 O O 2 1 2 OH 3 5 34 2 5 H HO 2 HO H HO CH2OH 5 H HO 4 3 4 2 H CH OH H OH H OH H O H CH2OH 34 2 OH H 1 5 OH H 1 HOH2C H furanose 6 OH

1 H CH2OH 6 H 6 2 O OH 5 H H OH H H O OH 3 6 1 O HO H 5 2 H H 34 5 4 2 HOH2C CH2OH H HO 2 H HO H 4 OH OH OH H O HO HO CH2OH 5 4 3 CH2OH 3 H OH 1 1 278 6 HO H OH H CH2OH pyranose

126 25.11: Deoxy . Carbohydrates that are missing a . 1 1 CHO CHO 2 H 2 OH H H HOH C OH HOH2C OH 3 2 O 3 O H OH H H H OH H H 4 4 H OH H H H OH H H H OH OH 5 OH 5 CH2OH CH2OH

D-ribose 2-Deoxy-D-ribose

1 1 CHO CHO 6 6 HO 2 H H HO 2 H H 3 5 3 5 O H OH H O OH H OH H OH CH OH CH3 4 4 2 4 4 H OH H HO 2 H OH H HO 2 5 H 5 H HO H HO 3 HO H HO 3 6 1 6 1 CH2OH OH H CH3 OH H L-Galactose 6-Deoxy-L-Galactose () 23.12: Amino Sugars. Carbohydrates in which a hydroxyl group is replaced with an -NH2 or -NHAc group

HOH2C HOH2C HO HO O O HO O OH HO C OH HN 2 HN CH H 3 H O O N-acetyl-D-glucosamine 279 N-Acetylmuramic acid (GlcNAc or NAG) (MurNAc)

23.13: Branched-Chain Carbohydrates. (Please read) 23.14: : The Fischer Glycosylation. Acetals and ketals of the cyclic form of carbohydrates.

O H+ + HO OR2 H , R2OH R2O OR2 + R2OH R1 H R1 H R1 H

hemiacetal acetal CHO H OH HOH C HOH C 2 2 HOH C HO H HO HO 2 O ROH O HO H OH HO HO + O OH H+ OR HO H OH HO HO H HO CH OH H H 2 OR pyranose D-glucose (hemiacetal)

acid-catalyzed mechanism: Mechanism 23.2, p. 967 280 Note that only the anomeric hydroxyl group is replaced by ROH

127 23.15: Disaccharides. A glycoside in which ROH is another carbohydrate unit (complex carbohydrate). OH HO OH OH HO HO HO HO OH O O O OH HO HO HO HO O H OH O HO HO HO O O HO HO O O O H HO HO O H O HO HO OH OH HO OH HO OH HO (1,2'-glycoside) OH (1,4'-α-glycoside) (1,4'-β-glycoside) (1,4'-β-glycoside)

23.16: Polysaccharides. : 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 : 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 281 HO HO HO HO HO O O HO HO HO

Amylopectin: Branched OH O HO O H OH amylose polysaccaride HO O HO O 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

23.17: Application of Familiar Reactions to Monosaccharides. (Table 23.2, p. 974) Reduction of Monosaccharides. C1 of aldoses are reduced with sodium borohydride to the 1° alcohol (alditols).

Reacts like a carbonyl CHO CH2OH HOH2C H OH H OH HO NaBH O HO H 4 HO H HO H OH H OH HO H OH H OH OH CH2OH CH2OH

D-glucose D-glucitol 282

128 CH OH CH OH Reduction of ketoses 2 CH2OH 2 O H OH HO H

HO H NaBH4 HO H HO H + H OH H OH H OH H OH H OH H OH CH OH 2 CH2OH CH2OH D-fructose D-glucitol D-mannitol Cyanohydrin formation CN CN CHO H OH HO H HO H HCN HO H HO H H OH + H OH H OH H OH H OH H OH CH2OH CH2OH CH2OH D-arabinose Acylation of the Hydroxyl Groups (ester formation):

H3C O O O O HO O H3C O CH3 H C HO O 3 HO O O OH O CH HO O 3 pyridine H3C O O O β-D-glucopyranose O CH3 O O O O OH OH O CH3 CH3OH, HCl H C O CH HO HO 3 3 H3C O O O HO HO O O OH HO HO pyridine H3C O 283 OCH 3 O OCH3 O CH3

O Alkylation of Hydroxyl Groups ( formation) HH O C HO H3CO Ag O, CH I H3CO + H OCH HO 2 3 H3O H CO H OCH3 O H CO 3 O HO 3 O H3CO OH H CO H3COCO H HO 3 OCH3 H CO H CO 3 3 OH H OOCHCH3 β-D-glucopyranose H OOHCH3 CCHH2OOCHCH3 HO PhH2CO KOH, PhCH Br HO 2 PhH CO O 2 O HO PhH2CO HO PhH2CO OCH3 OCH3 Acetal formation

HO Ph O O HO PhCHO O HO O HO ZnCl HO 2 HO OH OH

Furanose – pyranose isomerization

CHO HO O H OH OH H OH O OH HO H OH OH OH CH2OH OH OH D-ribopyranose D-ribose D-ribofuranose 284

129 Enolization and Epimerization

O HO , OH HO , O H O from 2 H2O CH2CH3 CH2CH3 CH2CH3 C6H5 C6H5 C6H5 Ch 20.2 CH3 H CH3 H3C H

O OH O H H H C C C (R) (S) H OH OH HO , HO H HO , HO H HO H H2O HO H H2O H OH H OH H OH H OH H OH H OH

CH2OH CH2OH CH2OH D-glucose D-mannose HO , H2O Aldose to ketose CH2OH isomerization O HO H H OH H OH

CH2OH D-fructose

285

Retro- of carbohydrates

CH2OH CH2OH O O H O CH2OH H-B CH2OH HO H HO H H OH + O O H O H H O :B CH OH HO H CH2OH H OH 2 H OH CH2OH CH2OH D-Glyceraldehyde Dihydroxyacetone D-fructose

23.18: Oxidation of Monosaccharides. C1 of aldoses can be

selectively oxidized to the (aldonic acids) with Br2 or Ag(I) (Tollen’s test).

CO2H HOH2C HOH2C H OH HO Br2 HO H2O O O HO H HO HO H OH HO HO H OH OH O CH2OH

CHO CO2H H OH Ag(I) Ag(0) H OH HO H HO H H OH H OH NH 3 , H OH H OH H2O CH2OH CH2OH 286 aldonic acid

130 Reducing sugars: carbohydrates that can be oxidized to aldonic acids.

HO HO HO HO HO HO HO HO HO O 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

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 lactose is a β end HO HO Ag(I) HO O HO No reaction HO 1 α [O] 2' glucose O β O sucrose is not OH fructose sucrose HO a reducing sugar (1,2'-glycoside) No reducing end 287 OH

Oxidation of aldoses to aldaric acids with HNO3.

CHO CO2H

H OH H OH CO2H HNO HO H 3 HO H HO HO O H OH H OH H OH H OH HO O CH2OH CO2H Glucaric acid

Uronic Acid: Carbohydrate in which only the terminal -CH2OH is oxidized to a carboxylic acid.

CHO CHO H OH H OH HO2C [O] HO HO H HO H O HO H OH H OH H OH H OH HO OH CH2OH CO2H Gluronic acid

Periodic Acid Oxidation. The vicinal diols of carbohydrate can be oxidative cleaved with HIO4. 288

131 Kiliani-Fischer Synthesis: chain lengthening of monosaccharides

289

Symmetry

Monarch butterfly: bilateral symmetry= mirror symmetry Mirror Mirror symmetry & symmetry axis (6 fold) of symmetry

Whenever winds blow butterflies find a new place on the willow tree -Basho (~1644 - 1694)

Point (center) of symmetry 290

132 Determination of carbohydrate stereochemistry

1) HCN CHO 2) H , Pd/BaSO 2 4 H OH 3) H2O H OH

CH2OH D-(-)-erythrose

CHO H OH Killiani-Fischer synthesis CH2OH D-(+)-glyceraldehyde

CHO HO H H OH 1) HCN CH2OH 2) H2, Pd/BaSO4 3) H2O D-(-)-threose

291

1) HCN CHO 2) H , Pd/BaSO 2 4 H OH 3) H2O H OH H OH

CH2OH D-(-)-ribose CHO H OH Killiani-Fischer H OH synthesis

CH2OH D-(-)-erythrose

CHO HO H H OH 1) HCN H OH 2) H2, Pd/BaSO4 3) H2O CH2OH D-(-)-arabinose

292

133 1) HCN CHO 2) H , Pd/BaSO 2 4 H OH 3) H2O HO H H OH

CH2OH D-(+)-xylose CHO HO H Killiani-Fischer H OH synthesis

CH2OH D-(-)-threose

CHO HO H HO H 1) HCN H OH 2) H2, Pd/BaSO4 3) H2O CH2OH D-(-)-lyxose

293

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

294

134 23.24: Glycosides: Synthesis of Oligosaccharides Mechanism 23.3: p. 980 HO AcO

AcO AcO AcO O AcO O AcO OCH3 AcO O HBr AcO AcO AcO O AcO O AcO AcO OAc Ag2O, base AcO O AcO AcO AcO OCH AcO 3 Br 23.25: Glycobiology (please read) : 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 295 asparagine

Chapter 24: Lipids. Hydrophobic (non-polar, soluble in organic solvent), typically of low molecular weight compounds of organic origin.

• fatty acids and waxes • essential oils • many vitamins • hormones (non-peptide) • components of cell membranes (non-peptide)

Share a common biosynthesis that ultimately derives their carbon source from glucose ()

Glucose → pyruvate → lactate

CHO H OH O O OH O HO H H3CC C O H3CC C O H OH H H OH CH OH 2 296

135