Carbohydrates.

Answers

Daniel Palleros

Carbohydrates. Additional Problems Answers

Problem 1
a), b)
H3C HO OH HO O OH CH3 OH OH HO O OH

1C more stable

C1 less stable

The 1C chair is more stable because it has more substituents in equatorial than the C1 chair. c) To go from the chair to the Fischer projection we follow these steps:
6
H3C

5
O HO

1
OH OH

5 cut bond between C1 and O

H 3C OH

H O OH

4
OH

4
OH

HO

rotate C4-C5 counterclockwise

OH CH3 H OH OH OH OH O OH

all carbons in the same plane

HO

H CH3 O OH

turn vetical; up goes left in Fischer down goes right in Fischer

CHO HO H H HO CH3 H OH OH H

Fischer projection

d) The anomeric OH is down in the chair, so it must go right in the closed Fischer projection.

Carbohydrates. Answers

2
H
HO H H O CH3

Daniel Palleros

OH
H OH

on opposite sides: !
OH H

e) Haworth projection
O CH3 OH OH OH OH

f) It is the L enantiomer of fucose. The OH on C5 is on the left. g) It is the anomer because the anomeric OH and the oxygen on the farthest stereogenic carbon (on C5) are on opposite sides. h) Fucose is an aldose. The carbonyl is on C1. i) Fucose is a deoxy sugar on C6. The stereogenic carbons have the opposite configuration from those of D-galactose. Another name is 6-deoxy-L-galactose.

Problem 2
a)
CHO HO H H H OH OH CH2OH H HO HO CHO OH H H CH2OH

D-Arabinose

L-Arabinose

b) To form the five-membered ring (furanose form), C1 must react with the OH on C4.
CHO H HO HO OH H H CH2OH OH

5
CH2OH OH CHO

turn on its side

rotate C3-C4 bond

OH

1 3 2
OH

OH

CHO

3 2
OH

5 CH2OH form hemiacetal

anomeric OH and OH on C4 on the same side: ! anomer

L-Arabinose 4 5
OH

OH

3
CH2OH

1 2
OH

!-L-arabinofuranose

Carbohydrates. Answers

Daniel Palleros

Closed Fischer projection:

HO H

OH

HO

same side: ! anomer

H CH2OH

c) To form the six-membered ring (pyranose form), C1 must react with the OH on C5.
CHO H HO HO OH H H CH2OH OH

5
CH2OH OH CHO

5
OH

turn on its side

OH

form hemiacetal

1
OH

1 3 2
OH

2
OH

anomeric OH and OH on C4 on opposite sides: ! anomer

!-L-arabinopyranose

L-Arabinose

Closed Fischer projection:

H H HO HO OH OH H H H2C O

opposite sides: ! anomer

Chair conformations:
OH O HO OH OH OH HO OH O OH

C1

1C

Carbohydrates. Answers

Daniel Palleros

Problem 3
a) -D-2-deoxyribopyranose
Closed Fischer projection
CHO H H H H OH OH CH2OH H H H H H 2C OH H OH OH O

same side: ! anomer

D-2-deoxyribose

D-2-deoxyribopyranose

b) Haworth projection
O

OH OH

OH

c) The most stable chair is 1C because more substituents are equatorial than in the C1 chair.
O HO OH OH HO OH O OH

C1

1C most stable

Problem 4
Epimers of galactose: Glucose; gulose and talose.

Problem 5
Before performing the rotations, it is helpful to number the carbons. For the 120o rotation along the vertical axis: down down up up equatorial equatorial axial axial

Carbohydrates. Answers

Daniel Palleros

120o

6 4
HO CH2OH O

2 1
HO

4 3
O OH

5 3
OH

6
CH2OH

OH OH

1
OH

OH

For the 180o rotation along the axis that cuts through C2-C3 and C5-O bonds: down up up down equatorial equatorial axial axial right left left right front front back back
6 4
HO CH2OH O OH OH O

5 3
OH

1 2 180o 1
OH OH HO

6
CH2OH OH

Problem 6
a) The two compounds are anomers.
OH

3
O

2
OH

180o

OH

HO O

1
OH

1 4
OH

OH

3
OH

II

chair filp 4
HO HO

5 OH O
OH

2 3

4
HO HO

5 OH O 2 3 1
OH

II

anomers

Carbohydrates. Answers

Daniel Palleros

b)
on the same side: ! anomer on opposite sides: " anomer
HO HO HO H

H HO HO H

1 2 3 4 5 CH2O

OH H H OH

1 2 3 4 5 CH2O

H H H OH

I
!-D-Lyxopyranose

II
"-D-Lyxopyranose

Problem 7

If we rotate structure I 180o along the vertical axis, structure II is obtained. I and II represent the same compound. In this rotation, for the atoms directly attached to the ring: up up down down right left left right front back back front
180o 6
HO

6
OH HO

H OH O OH OH

2
OH

HO

1 1 2

3
O

5 4

OH

OH

II

Problem 8
When trying to identify a sugar molecule we must first locate the two most important carbons: the anomeric carbon and the carbon that makes the sugar D or L (the farthest stereogenic carbon). The anomeric carbon is the carbon attached to two oxygens. If the anomeric carbon is directly attached to a hydrogen atom and only one other carbon, the sugar is an aldose, but if it is attached to two carbons, it is a ketose.

Carbohydrates. Answers

7
anomeric C anomeric C

Daniel Palleros

OH

OH OH

hydrogen attached to only one C ! aldose attached to two C ! ketose

To decide between D and L series it is helpful to remember that, in general, the farthest stereogenic center is R for D sugars and S for L sugars (this is true as long as the priority of the groups follows the order shown below).
2
H HO

2
C OH H CH2OH

HO H

H OH

4 R

CH2OH

3 D sugar

3 S L sugar

After those two carbons have been identified, the carbons must be numbered to decide whether it is a pentose, hexose, etc. Lets consider structure I:
farthest stereogenic C 4
HO

5 2

1 3
OH OH OH

anomeric C

down R D series

I
same side: ! anomer

It has five carbons: pentose Six-membered ring: pyranose Anomeric carbon, C1, attached to only one other carbon: aldose

Carbohydrates. Answers

Daniel Palleros

The farthest stereogenic carbon is C4. The OH on C4 is going down in the chair, that implies it goes on the right in the Fischer projection, the sugar is D. Further confirmation shows that it has R stereochemistry. The anomeric OH and the OH on C4 are both on the same side: anomer. Lets consider structure II:
OH

S anomeric C 5 2 3 6
OH OH O OH

4
HO

II
CH2OH and OH trans: ! anomer

Hexose Pyranose Aldose Farthest stereogenic carbon: C5; CH2OH group pointing down in chair: L series. Confirmed by S stereochemistry for C5. Anomeric OH and free CH2OH are trans: anomer. Lets consider structure III Lets rotate the molecule 180o along the axis that goes through the oxygen and cuts through C2-C3.
S
H O H H OH HO H HO

1
HO

6 5 4
H H O OH

OH

4 2
HO

anomeric C

3
H

5 6
OH

OH

rotate 180o

1
H

3
HO

2
H

III

III

Hexose Furanose Aldose Farthest stereogenic carbon: C5; S stereochemistry: L series. In the L series the OH on the farthest stereogenic center is on the left in the Fischer projection. The anomeric OH in structure III is up, which corresponds to left in the Fischer projection; thus, this is the anomer. Another way of seeing it: L sugar, anomeric OH up => (3rd definition of anomers).

Carbohydrates. Answers

Daniel Palleros

Lets consider structure IV

H O

OH

4
HO

1
OH

H H

anomeric C

5 6
OH

3
HO H

2 H

IV
Hexose Furanose Aldose Farthest stereogenic carbon: C5; S stereochemistry: L series. In the L series the OH on the farthest stereogenic center is on the left in the Fischer projection. The anomeric OH in structure IV is up, this corresponds to left in the Fischer projection; thus, this is the anomer. According to the 3rd definition of anomers: L sugar, anomeric OH up => . Notice that structures III and IV are identical in all respects except for the position of the side chain C5-C6 which is up in III and down in IV. Note, however, that both structures belong to the L series. The stereochemistry of C4 defines whether the C5-C6 chain is up or down, but it is the stereochemistry of C5 that decides the series. Lets consider structure V
R
HO

6
O

OH

2 3 1
OH OH

4
OH

anomeric C

V
Hexose Furanose Ketose (the anomeric carbon is C2) Farthest stereogenic carbon: C5; R stereochemistry: D series. In the D series the OH on the farthest stereogenic center is on the right in the Fischer projection; the anomeric OH in structure V is up, this corresponds to left in the Fischer projection, thus, this is the anomer. According to the 3rd definition of anomers: D sugar, anomeric OH up => .

Carbohydrates. Answers

10

Daniel Palleros

Lets consider structure VI Lets rotate it 180o along the axis that cuts through C2-C3 and C5-O bond, to have it in the standard representation.
HO

6
CH2OH OH O

HO

1
O

6 5 3 OH
OH OH CH2OH

rotate 180o

5
HO

anomeric C

1
OH

VI Hexose Pyranose Aldose Farthest stereogenic carbon: C5; free CH2OH up, D series; also confirmed by R stereochemistry for C5. In the D series the OH on the farthest stereogenic center is on the right in the Fischer projection; the anomeric OH in structure VI (after rotation; standard representation) is down, this corresponds to right in the Fischer projection, thus, this is the anomer. According to the second definition of anomers: terminal CH2OH and anomeric OH, trans => anomer

Problem 9
a) Glucuronides or glucuronosides are glycosides in which the glycone is glucuronic acid.
COOH O HO HO OH OH HO HO OH OR COOH O

!-D-glucuronic acid

a glucuronide: R ! H

b) A phenolic mannoside:
CH2OH HO HO OH O O OH

!-D-mannose

a phenol

Carbohydrates. Answers

11

Daniel Palleros

c) Example: D-2-deoxyribose
CHO CH2OH H H H H H OH H OH HO CH2OH H H O H OH

! anomer

D-2-deoxyribose

2-deoxy

d) Example: glucosamine
CHO OH H HO H H NH2 H OH OH CH2OH O HO HO NH2 OH

! anomer

2-amino-2-deoxy-D-glucose (glucosamine)

2-amino-2-deoxy

Problem 10
a) Glucuronides contain glucuronic acid which is a carboxylic acid, pKa 4-6:
COOH O HO HO OH OR HO HO OH OR

pKa 4-6

COO O

a glucuronide: R ! H

at pH > pKa

At the pH of urine (pH 5.6-7) the glucuronic acid is dissociated (pH > pKa) and thus, the solubility of the glucuronide is increased.

Carbohydrates. Answers

12

Daniel Palleros

b) Sialic acid has a carboxylic acid group, pKa 4-6. At the pH of the blood (pH 7.4) the carboxylic acid is completely dissociated increasing the hydrophilicity of the cells to which it is attached.
HO HO AcHN HO OH OH O COOH HO HO AcHN OH O HO COO OH

pKa 4-6

at pH 7.4

Problem 11
Cellobiose ( anomer): 4-O-(-D-glucopyranosyl)--D-glucopyranose or in shorthand notation: -D-Glcp(14)-D-Glcp
OH OH O HO HO OH O HO OH OH
cellobiose

Maltose ( anomer): 4-O-(-D-glucopyranosyl)--D-glucopyranose or in shorthand notation: -D-Glcp(14)-D-Glcp

OH O HO HO OH O HO OH OH OH O

maltose

Lactose ( anomer): 4-O-(-D-galactopyranosyl)--D-glucopyranose or in shorthand notation: -D-Galp(14)-D-Glcp

OH OH O HO OH O HO OH OH O OH

lactose

Carbohydrates. Answers

13

Daniel Palleros

Sucrose: 2-O-(-D-glucopyranosyl)--D-fructofuranoside or in shorthand notation: -D-Glcp(12)-D-Fruf

OH O HO HO OH OH O O OH CH2OH OH
sucrose

Problem 12
-L-Fucp(12)-D-Galp(13)-D-GalpNAc(13)-D-Galp (14)-D-Galp(14)-D-Glcp

Problem 13
OH O OH O O HO OH O HO NHAc OH O OH OH OH CH2OH

Problem 14 a)
amygdalin

OH O HO HO OH O HO HO OH O CN O

OH

H3O+
O HO OH OH
a cyanohydrin +

CN

HO HO

Carbohydrates. Answers

14

Daniel Palleros

Cyanohydrins decompose to aldehydes (or ketones) plus H-CN (hydrogen cyanide) which is highly toxic.

HO

CN

BHB

CN

+ B-

CN HB

highly toxic

HCN

b) The shorthand notation for amygdalin: -D-Glcp(16)-D-Glcp