Jones M., Fleming S.A. Organic Chemistry

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22.2 Nomenclature and Structure of Carbohydrates 1129

D-Ribose D-Arabinose

D-Xylose D-Lyxose

OHH

CHO

HHO

CHO

OHH

CHO

HHO HHO

HHO

CHO

FIGURE 22.7 The four

D-aldopentoses and their

common names.

Four-carbon sugars are called tetroses. There are four possible aldotetroses,

which are four-carbon sugars with an aldehyde (Fig. 22.6).The aldotetroses are the

enantiomeric pair

D- and L-erythrose and the enantiomeric pair D- and L-threose.

Remember, for a carbohydrate to be

D, the OH of the configurational carbon must

be on the right-hand side of a Fischer projection.

D-Erythrose L-Erythrose

OHH

CHO

HHO

CHO

D-Threose L-Threose

OHH

HHO

CHO

HHO

OHH

CHO

WEB 3D WEB 3D

FIGURE 22.6 The four aldotetroses.

Aldopentoses are five-carbon aldoses.These carbohydrates contain three stereogenic

carbons, and so there must be a total of eight stereoisomers (2

 8). Figure 22.7 shows

the four members of the

D series of aldopentoses and their common names.

Aldohexoses are six-carbon aldoses. They have four stereogenic carbons and so

there must be a total of 2

 16 stereoisomers, eight in the D series (Fig. 22.8) plus

OHH

CHO

HHO

CHO

OHH

CHO

HHO HHO

HHO

CHO

OHH

OHH OHH OHH OHH

CHO

HHO

CHO

OHH

CHO

HHO HHO

HHO

OHH HHO

CHO

HHO

OHHHHO

D-Allose D-Altrose D-Glucose D-Mannose

D-Gulose D-Idose D-Galactose D-Talose

WEB 3D WEB 3D

FIGURE 22.8 The eight

D-aldohexoses and their

common names.

the eight L enantiomers of these molecules. Each carbon of an aldose is numbered

starting with the aldehyde carbon as C(1), as shown for allose in Figure 22.8.

Figures 22.7 and 22.8 show only aldopentoses and aldohexoses,but there are also

many keto sugars among the pentoses, the five-carbon carbohydrates, and the

hexoses,the six-carbon carbohydrates.Figure 22.9 shows

D-fructose, the most com-

mon ketohexose.

1130 CHAPTER 22 Carbohydrates

D-Fructose

OHH

HHO

OHH

This ketone

makes fructose

a ketohexose

WEB 3D

FIGURE 22.9 D-Fructose,

a ketohexose.

PROBLEM 22.4 Draw Fischer projections for the L-aldopentoses and use Figure 22.7

to provide the common name for each.

PROBLEM 22.5 How many D-aldoheptoses are possible?

PROBLEM 22.6 Treatment of D-glucose (Fig. 22.8) with sodium borohydride

(NaBH

) gives D-glucitol (sorbitol), C

. Draw the three-dimensional

structure of D-glucitol and write a brief mechanism for this reaction.

One would expect aldoses to combine the chemistries of alcohols and aldehydes,

and that expectation is correct. In fact, the proximity of these functional groups

leads to important intramolecular chemistry, and here is an example. Although

reduction of glucose with sodium borohydride followed by hydrolysis induces the

expected change (see Problem 22.6), modern spectroscopic methods such as NMR

and IR do not reveal the presence of substantial amounts of the aldehyde in the

starting carbohydrate (Fig. 22.10). It is important to understand why this is so.

The chemistry of the aldose tells us there is an aldehyde and we certainly have been

drawing an aldehyde group in our Fischer projections. So why can’t we observe the

aldehyde spectroscopically?

D-Glucose

OHH

NaBH

HHO

D-Glucitol

(~ 65%)

OHH

HHO

But

D-glucose has:

1. No large peak in IR for C

2. No peak in

H NMR for H

FIGURE 22.10 Although reduction

with sodium borohydride, followed

by hydrolysis, proceeds normally to

give an alcohol, neither NMR nor IR

spectroscopy reveals large amounts of

an aldehyde in the starting material.

22.2 Nomenclature and Structure of Carbohydrates 1131

You know already that carbonyl groups react with all manner of nucleophiles

(Chapter 16).Hydration and hemiacetal formation are typical examples (Fig. 22.11).

A hemiacetal could certainly be formed in an intramolecular reaction in which a

hydroxyl group at one location in a molecule reacted with a carbonyl group at another

location.Indeed,4- and 5-hydroxy aldehydes exist mostly in the cyclic hemiacetal forms

(p. 783). Figure 22.11 shows a typical reaction of this kind and makes the analogy

to both hydration and intermolecular hemiacetal formation.

Hydration

Hemiacetal formation

Intramolecular hemiacetal formation

HOR

Cat. H

5-Hydroxyhexanal

(6%)

2-Hydroxy-6-methyl-

tetrahydropyran

A cyclic hemiacetal

(94%)

FIGURE 22.11 Intramolecular hemiacetal formation is analogous to hydration

and intermolecular hemiacetal formation. Cyclic hemiacetals having five or

six atoms in the ring are easily made and are often more stable than their

open forms.

The key to the solution of the “missing aldehyde” problem is that for hexoses in an

aqueous environment the hemiacetal form is more stable than the open-chain isomer.

We can even venture a reasonable guess as to which hydroxyl group of the carbohydrate

participates in the ring-forming reaction.For the cyclic hemiacetal to be more stable than

the acyclic hydroxy aldehyde, the ring formed surely must not introduce a lot of strain.

That eliminates three of the five OH groups and points to either the OH at C(4), which

leads to a five-membered ring, or the OH at C(5), which produces a six-membered ring

1132 CHAPTER 22 Carbohydrates

Cyclic forms of carbohydrates are named by replacing the -se at the end of the

name of the carbohydrate with -furanose or -pyranose to indicate the size of the ring.

D-Glucofuranose and D-glucopyranose can be drawn in Fischer projection and in the

more common line representation (Fig. 22.13). Notice that the

D-glucopyranose line

An aldohexose

A furanose

A pyranose

Tetrahydrofuran

CHO

close with

OH at C(4)

close with

OH at C(5)

HCOH

Tetrahydropyran

O O

C(4)

C(5)

HCOH

FIGURE 22.12 In an aldohexose,

intramolecular hemiacetal formation

results in either a furanose (five-

membered ring) or a pyranose (six-

membered ring).

close with

OH at C(4)

close with

OH at C(5)

D-Glucose

OHH

D-Glucofuranose

D-Glucopyranose

O H

FIGURE 22.13 Fischer projections and

corresponding line representations for

D-glucofuranose and D-glucopyranose.

The squiggled bond means that both

stereoisomers are possible.

(Fig. 22.12).These cyclic forms are named as furanoses (cyclic carbohydrates having a

five-membered ring) or pyranoses (cyclic carbohydrates having a six-membered ring) by

analogy to the five- and six-membered cyclic ethers: tetrahydrofuran and tetrahydropyran.

22.2 Nomenclature and Structure of Carbohydrates 1133

representation is shown with all groups but the “squiggled”one equatorial. This pic-

ture of

D-glucopyranose is very important.We can use it as a starting point for draw-

ing all other aldohexopyranoses. For example,

D-galactose differs from D-glucose at

C(4) (Fig. 22.8), and as a result the OH at the C(4) position in the chair structure

for

D-galactopyranose is axial rather than equatorial.When two sugars, or any two mol-

ecules for that matter, differ only by the stereochemistry at one carbon they are called

epimers. D-Galactose and D-glucose, for example, are epimers, or C(4) epimers.

PROBLEM 22.7 Draw Fischer projections for D-galactofuranose, D-mannopyranose,

and L-gulopyranose (see Fig. 22.8).

Both furanoses and pyranoses are formed from most aldohexoses, but it is the six-

membered rings that usually predominate (Table 22.1). We’ll prove this point a little

later in this chapter, but for now accept that this claim is reasonable, and let’s go on to

TABLE 22.1 Ratios of Pyranose and Furanose Forms

of Aldohexoses at 25 °C in Water

Aldohexose Pyranose Form (%) Furanose Form (%)

Allose 92 8

Altrose 70 30

Glucose 100

Mannose 100

Gulose 97 3

Idose 75 25

Galactose 93 7

Talose 69 31

deal with the question of why typical carbonyl reactions (Fig. 22.11) are observed for

these cyclic hemiacetals. There is a simple answer to this puzzling question. The mol-

ecule isn’t locked 100% in the cyclic form, it just exists predominantly in that form. It is

in equilibrium with a small amount of the acyclic isomer, which does contain a carbonyl

group and does react with reagents such as sodium borohydride. As the small amount

of the reactive carbonyl form is used up, more of it is generated (Fig.22.14). Sugars that

are in the hemiacetal form,and are therefore in equilibrium with an open form,are called

reducing sugars. We will soon see the chemistry responsible for this descriptive term.

OHH

CHO

OHH

Pyranose form

(> 99.95%)

Open form

(< 0.05%)

D-Glucose

NaBH

As long as an equilibrium exists,

more open form will be generated

as the reduction takes place

OH +

FIGURE 22.14 If two compounds are

in equilibrium, irreversible reaction of

the minor partner can result in

complete conversion into a product.

As long as the equilibrium exists, the

small amount of the reactive molecule

will be replenished as it is used up.

Table 22.1 lists some common carbohydrates and gives the relative amounts

found in pyranose and furanose forms in aqueous solutions. There is very little of

the open form present at equilibrium. There is a clear preference for the pyranose

1134 CHAPTER 22 Carbohydrates

rings over the furanose forms, presumably because of the thermodynamic stability

of the six-membered ring chair structures (p. 190).

However, because there is always a small amount of the reducible open form

present, all of the material can eventually be reduced by sodium borohydride. If

we return to our spectrometers, crank up the sensitivity, and look very hard for the

aldehyde group present in the open-chain form, there it is, in the tiny amount

required by our explanation.

Let’s turn our attention to the structure of the

D-glucopyranoses.The OH of C(5)

bonds with the carbonyl C.The carbonyl O becomes an OH on C(1) and the O from

the C(5) OH is the ring O.The first thing to notice is that the intramolecular cycliza-

tion reaction creates a new stereogenic carbon at C(1) that can be either (R) or (S).

Addition of the nucleophilic OH of C(5) can occur from two possible faces of the alde-

hyde.The resulting isomers are called anomers and the C(1) carbon is called the anomer-

ic carbon.Anomers of aldoses differ only in the stereochemistry at the anomeric carbon.

If the OH on the anomeric carbon is on the same side in Fischer projection as the OH

on the configurational carbon, it is the α anomer. If it is on the opposite side, it is the β

anomer. The stereoisomers are shown in Fischer projections and in the more accurate

chair structures in Figure 22.15, which also shows the schematic “squiggly bond” used

to indicate that the new OH group at the anomeric carbon can be on the right or left

in the Fischer projection, which is axial or equatorial in the chair structure.

topside

attack

bottomside

attack

D-Glucose

α Anomer

β Anomer

“Squiggle” indicates

both α and β anomers

are present

D-Glucopyranose

FIGURE 22.15 Intramolecular hemiacetal formation results in two C(1) stereoisomers called anomers shown in Fischer

projection and as chair structures.The α anomer has the OH on the anomeric carbon on the same side of the Fischer

projection as the OH of the configurational carbon.The β anomer has the OH on the anomeric carbon on the opposite side

of the OH of the configurational carbon.

PROBLEM 22.8 Identify the new stereogenic carbon in the α and β anomers of

Figure 22.15 as either (R) or (S).

22.2 Nomenclature and Structure of Carbohydrates 1135

Both α- and β-pyranose and furanose forms exist.Table 22.2 shows the relative

amounts for the aldohexoses in aqueous solution.

CONVENTION ALERT

TABLE 22.2 ␣- and ␤-Pyranose and Furanose Forms of the Aldohexoses at

25 °C in Water

Aldohexose α-Pyranose β-Pyranose α-Furanose β-Furanose

Form Form Form Form

Allose 16 76 3 5

Altrose 27 43 17 13

Glucose 36 64

Mannose 66 34

Gulose 16 81 3

Idose 39 36 11 14

Galactose 29 64 3 4

Talose 37 32 17 14

6161

OHH

“Squiggly” bond

indicates both

stereoisomers

(both anomers)

are present

“Around the

corner” bond

␤-D-Glucofuranose

D-Glucofuranose

␣-D-Glucofuranose

(a) (b)

FIGURE 22.16 In Fischer projections, we have drawn “around the corner” bonds. The more common

line representations for

D-furanose and D-pyranose forms have the OH on the anomeric carbon down

for the α anomer and up for the β anomer.

The last few figures have shown Fischer projections with some very peculiar

bonds. Notice in particular the “around the corner” bonds sometimes used to

show attachment to the ring oxygen (Fig. 22.16a). The squiggly bond is used

to show that both anomers can be present (Fig. 22.16b). Because we usually work

with

D sugars and because we normally draw line representations of the pyranoses

and furanoses, it has become conventional to describe the α anomer as having

the OH on C(1) down as shown in Figure 22.16.The β anomer in a D sugar has the

OH on C(1) up.

We know that bonds do not go around corners,so let’s see how we convert a Fischer

projection into a chair structure.There are many ways to do this task, and any way you

devise will do as well as the following method. Just be certain that your method works!

We will continue to use

D-glucose as an example and work through a method of arriv-

ing at a three-dimensional structure.

1136 CHAPTER 22 Carbohydrates

First, redraw the Fischer projection (Fig. 22.17a) so that the horizontal lines are

wedges coming out of the plane of the paper (Fig. 22.17b). Second, rotate the mol-

ecule 90° clockwise and redraw it with C(1) at the far right of the molecule and going

away from the plane of the paper (Fig. 22.17c).Third, rotate the carbon–carbon bond

to position the OH that will contribute its O to the ring so that it is pointing toward

the C(1) carbon. If a pyranose is being formed, then it is the OH on C(5) that con-

tributes the ring oxygen.Thus, this reaction requires rotation around the

bond (Fig. 22.17d). If a furanose is to be formed, then it is the OH on C(4) that con-

tributes the ring oxygen, and the rotation is around the bond. Redraw

the molecule with the contributing OH positioned so that it points toward C(1).Fourth,

make the pyranose (or furanose) ring by drawing a bond between C(1) and the O bond-

ed to C(5) [or to C(4)], and draw the C(1) OH down for the α anomer and up for the

C(3)

C(4)

C(5)

rotate

molecule

90° clockwise

rotate

C(4)¬C(5)

bond to make

pyranose

(a)

CHO

(b)

(c)

CHO

␣-D-Glucopyranose

D-Glucose

␤-D-Glucopyranose

(d)

ring

O O

FIGURE 22.17 Four steps to

transpose a Fischer projection into

the line representation called a

Haworth form.

β anomer or a squiggly line to indicate both.This kind of planar representation is called

a Haworth form, after its inventor, Walter N. Haworth (1883–1950). Figure 22.18

repeats the process, transposing

D-ribose into the α and β anomers of D-ribofuranose.

␤-D-Ribofuranose

rotate

molecule

90° clockwise

rotate

C(3)¬C(4)

bond to make

furanose

ring

OHH

CHO

OHH

CHO

␣-D-Ribofuranose

OHOH

D-Ribose

HOCH

OH CH

FIGURE 22.18 Constructing the

Haworth forms of the α and β

anomers of

D-ribofuranose.

22.2 Nomenclature and Structure of Carbohydrates 1137

PROBLEM 22.9 Draw the Haworth form of (a) the α anomer of D-glucofuranose;

(b) β-D-ribofuranose, which is the sugar in ribonucleic acid (RNA); and

D-2-deoxyribofuranose, the sugar in deoxyribonucleic acid (DNA).

Of course, there are two chair forms, but the one with four equatorial groups is

the more stable one.

PROBLEM 22.11 Transform the Fischer projection of D-mannose (Fig. 22.8) into

the chair structure of β-

D-mannopyranose using the method described in Figures

22.17 and 22.19. Confirm your answer by using the fact that D-mannose is the

C(2) epimer of D-glucose.

␤-D-Glucopyranose

pull down

pull up

flip

WEB 3D

FIGURE 22.19 The Haworth form of a pyranose is much more accurately shown as a chair structure.

Don’t forget that there are always two possible chair forms.

WORKED PROBLEM 22.10 Transpose the Haworth form of α-D-glucopyranose

(Fig. 22.17) into the chair structure.

ANSWER In the α anomer, the hydroxyl group at C(1) is axial, not equatorial as

in the β anomer. Otherwise all the substituent groups of the α anomer remain

equatorial.

pull down

HO OH

HOCH

C(1)

pull up

(more stable)

(less stable)

flip

Six-membered rings are not flat; they exist in energy-minimum chair forms.The

final step in this exercise therefore is to allow the flat Haworth form to relax to a

chair (Fig. 22.19). There are two chairs possible for any six-membered ring. They

are interconverted by the rotations around carbon–carbon bonds we called a ring flip

(p. 192). Be sure to check both forms to see which is lower in energy. Sometimes

this evaluation will be difficult, but for β-

D-glucopyranose, it is easy. The form with

all groups equatorial will be far more stable than the one with all groups axial.

Summary

Carbohydrate names specify: (1) the length of the carbon chain, (2) whether the

molecule is an aldehyde or ketone, (3) whether the configurational carbon is

D or

L, (4) whether the structure is a cyclic six-membered ring or five-membered ring,

1138 CHAPTER 22 Carbohydrates

and (5) whether the α or β anomer is formed.Some of you will be expected to mem-

orize the common names for all of the sugars, but all students of organic chemistry

should be able to draw a reasonable 3-D structure of β-

D-glucopyranose!

22.3 Formation of Carbohydrates

Nature has the process for making carbohydrates down to an art. Plants use a num-

ber of enzymes to produce sugars. For example, the enzyme ribulose-1,5-bisphos-

phate carboxylase/oxygenase (Rubisco) is used by plants to assimilate CO

from the

atmosphere. With the help of this enzyme, the sugar ribose becomes carboxylated

by the CO

and the resulting six-carbon molecule undergoes a reverse aldol reaction

to produce two molecules of glycerate that can be used to synthesize glucose, the car-

bohydrate used most frequently by living organisms to store chemical energy. Rubisco

is perhaps the most prevalent protein on Earth. Its ability to convert CO

into the

chemical form of energy (sugar) makes it a logical starting point for a Nature-based

solution to our burgeoning buildup of atmospheric CO

, a greenhouse gas.

22.3a Lengthening Chains in Carbohydrates Plants are not the only

sources of carbohydrates, as chemists are able to make sugars in the laboratory.

For example, treatment of

D-ribose with cyanide followed by catalytic hydro-

genation and hydrolysis generates the sugars

D-allose and D-altrose (Fig. 22.20).

NaCN H

/Pd

“poisoned”

OHH

D-Ribose

D-Altrose

C(1) becomes...

Not isolated

OHH

...C(2)

C(2)

OHH

HHO

OHH

HHO

CHO

D-Allose

OHH

CHO

Total yield 70–80%

OHH

HHO

Two new sugars, each

one carbon longer than

the starting sugar

FIGURE 22.20 The modern version

of the Kiliani–Fischer synthesis.