CARBOHYDRATES OR SUGARS
• A group of naturally occurring aldehydes / ketones,
formally composed of C atoms and H2O molecules
in a ratio equal or close to 1 : 1
general formula: (CH2O)n ... or close
• Immense biological importance of carbohydrates:
blood group determinants
antigens, immune responses
cancer cell markers
energy storage & generation
nucleic acids, glycoproteins
materials & fibers
extracellular support matrices
genetic disease
01 SIMPLE SUGARS OR MONOSACCHARIDES
• Carbohydrates of general formula (CH2O)n (3 ≤ n ≤ 9) that
possess a structure based on a linear polyhydroxy aldehyde
(aldoses) or polyhydroxy ketone (ketose)
HOCH2–(CHOH)x–CHO
an aldose
HOCH2–(CHOH)x–(CO)–(CHOH)y–CH2OH
a ketose
• Triose, tetrose, pentose, hexose, heptose, octose, nonose:
a monosaccharide that incorporates a total of 3, 4, 5, 6, 7,
8 or 9 carbon atoms
Note: most monosaccharides of biological importance contain 5 or 6 C atoms.
Monosaccharides incorporating more that 6 C atoms are known, but they
are rare, and rarity increases with an increasing number of C atoms.
02 STEREOISOMERISM IN MONOSACCHARIDES
• Monosaccharides as chiral molecules due to the presence
of multiple stereogenic centers
HOCH2–(CHOH)x–CHO
an aldose
HOCH2–(CHOH)x–(CO)–(CHOH)y–CH2OH
a ketose
• Common ketoses of biological interest as compounds
of the type HOCH2–(CHOH)x–(CO)–CH2OH
• The vast majority of naturally occurring monosaccharides
as chiral and enantiomerically pure substances
03 REPRESENTATION OF MONOSACCHARIDES
• Frequent use of Fischer projections to represent
monosaccharides; e.g.:
CHO
H
OH
H
OH
H
OH
OH
ribose
H
HO
H
H
CHO
OH
H
OH
OH
OH
glucose
HO
H
H
OH
O
H
OH
OH
OH
fructose
• Ribose as a pentose; glucose and fructose as hexoses
• Ribose and glucose as aldoses; fructose as a ketose
04 GLYCERALDEHYDE: THE SIMPLEST ALDOTRIOSE
• D- and L-forms of glyceraldehyde:
CHO
H
OH
OH
D-(R)-(+)-glyceraldehyde
(OH on the right)
enantiomers
CHO
H
HO
HO
L-(S)-(–)-glyceraldehyde
(OH on the left)
• D-Glyceraldehyde as the formal progenitor of all common
monosaccharides
05 STEREOCHEMICAL PROGENY OF COMMON ALDOSES
key stereogenic center
CHO
H
OH
H
OH
OH
erythrose
CHO
H
OH
H
OH
H
OH
OH
ribose
CHO
H
OH
OH
glyceraldehyde
(aldotriose)
CHO
H
HO
H
OH
OH
threose
(aldotetroses)
CHO
H
HO
H
OH
H
OH
OH
(aldopentoses)
arabinose
CHO
H
OH
H
HO
H
OH
OH
xylose
CHO
H
HO
H
HO
H
OH
OH
lyxose
(aldohexoses)
H
H
H
H
CHO
OH
OH
OH
OH
OH
allose
HO
H
H
H
CHO
H
OH
OH
OH
OH
altrose
H
HO
H
H
CHO
OH
H
OH
OH
OH
glucose
HO
HO
H
H
CHO
H
H
OH
OH
OH
mannose
H
H
HO
H
CHO
OH
OH
H
OH
OH
gulose
HO
H
HO
H
CHO
H
OH
H
OH
OH
idose
H
HO
HO
H
CHO
OH
H
H
OH
OH
galactose
HO
HO
HO
H
CHO
H
H
H
OH
OH
talose
06 D- AND L-MONOSACCHARIDES
enantiomeric
compounds!
CHO
H
OH
OH
D-(R)-(+)-glyceraldehyde
(OH on the right)
CHO
H
OH
H
OH
OH
D-erythrose
CHO
H
OH
H
OH
H
OH
OH
D-ribose
H
HO
H
H
CHO
OH
H
OH
OH
OH
D-glucose
CHO
H
HO
HO
L-(S)-(–)-glyceraldehyde
(OH on the left)
HO
H
HO
HO
HO
CHO
H
OH
H
H
CHO
H
HO
H
HO
H
HO
HO
L-ribose
CHO
H
HO
H
HO
HO
L-erythrose
L-glucose
• Most natural monosaccharides belong to the D-stereochemical series.
The much rarer L-sugars are produced primarily by fungal or microbial
organisms for specialized purposes
07 STRUCTURE OF MONOSACCHARIDES:
FORMATION OF HEMIACETALS
• Molecules incorporating both an alcohol and an aldehyde
or ketone functionality tend to exist as cyclic hemiacetals
— if a 5- or 6-membered ring can thus be formed; e.g.:
aldehyde or ketone
R
O
R
OH
O
OH
5- or 6-membered ring
08 HEMIACETAL FORMS OF D-RIBOSE AND D-GLUCOSE
wavy line means that either
configuration is possible
Ribose (building block of RNA):
CHO
H
OH
H
OH
H
OH
OH
Fischer projection
of D-ribose
H
HO
H
OH
CHO
HO
HO
OH
HO
aldehyde (carbonyl)
form of D-ribose
OH
O
OH
common hemiacetal form
of D-ribose (preferred)
Glucose:
H
HO
H
H
CHO
OH
H
OH
OH
OH
Fischer projection
of D-glucose
HO
H OH
HO
H
CHO
OH
OH
aldehyde (carbonyl)
form of D-glucose
HO
O
HO
OH
OH
OH
common hemiacetal form
of D-glucose (preferred)
09 FURANOSE AND PYRANOSE FORMS
OF MONOSACCHARIDES
O
O
O
O
furan
tetrahydrofuran
pyran
H
furanose form HO
of D-ribose
("D-ribofuranose")
H
O
OH
HO
O
HO
HO
OH
tetrahydropyran
OH
OH
pyranose form
of D-glucose
("D-glucopyranose")
OH
Anomeric position or anomeric carbon: the one
sustaining the hemiacetal function (arrows above)
10 POSSIBLE EXISTENCE OF TWO DIASTEREOMERS OF
THE HEMIACETAL FORM OF A MONOSACCHARIDE
alpha- and beta-anomers of a monosaccharide
anomeric carbon
H
HO
O
OH
H
HO
H
O
OH
HO
O
HO
HO
OH
!-anomer of
D-ribofuranose
(!-D-ribofuranose)
HO
OH
"-anomer of
D-ribofuranose
("-D-ribofuranose)
OH
OH
OH
!-anomer of
D-glucopyranose
(!-D-glucopyranose)
H
HO
O
HO
OH
OH
OH
"-anomer of
D-glucopyranose
("-D-glucopyranose)
alpha-anomer: the OH group of the hemiacetal moiety is trans relative to
the CH2OH group on the carbon that defines the D / L series
beta-anomer:
the OH group of the hemiacetal moiety is cis relative to
the CH2OH group on the carbon that defines the D / L series
11 CONFORMATIONS OF PYRANOSES; e.g., GLUCOSE
H
HO
H
O
HO
OH
OH
OH
"-D-glucopyranose
H
HO
O
HO
HO
HO
H
OH
!-D-glucopyranose
HO H
H
HO
HO
H
HO
H
H
OH
H HO
H
HO
all equatorial:
favored
OH
OH
OH
O
OH
H
OH
O
H
HO H
OH
H
all but 1 OH equatorial:
favored
OH H
H
O
A-value of OH < 1.0 kcal/mol
A-value of CH2OH ≈ 2 kcal/mol
HO
H
OH
H
H
H
H
O
HO OH OH
under appropriate condi7ons, it is possible to obtain pure α-­‐D-­‐glucopyranose or pure β-­‐D-­‐glucopyranose (crystalliza7on). These two anomeric forms of glucopyranose, being diastereomeric, differ in solubility, mel7ng point (146 °C for the α-­‐anomer, 150 °C for the β-­‐anomer), and op7cal rota7on ([a]D25 = +112° for the α-­‐anomer, + 19° for the β-­‐anomer). 12 INTERCONVERSION OF PYRANOSE AND FURANOSE
FORMS AND OF α- and β-ANOMERS: RIBOSE
O
HO
OH
b
OH
!-D-ribopyranose
O
HO
OH
OH
HO
a
HO
H
a
HO
HO
HO
H OH
O
OH
OH
!-D-ribofuranose
b
OH
"-D-ribopyranose
H
CHO
H
OH
H
OH
H
OH
OH
D-ribose
OH
O
OH
a
HO
CHO
OH
"-D-ribofuranose
b OH
all forms will be present at equilibrium in a solution of ribose, although
one especially thermodynamically favorable form may be the dominant
(or even the exclusive) species (β-D-ribofuranose in the this case)
13 INTERCONVERSION OF PYRANOSE AND FURANOSE
FORMS AND OF α- and β-ANOMERS: GLUCOSE
HO
H
HO
O
OH
b
HO
OH
!-D-glucofuranose (3)
HO
CHO
H
OH
HO
H
H
OH
H
OH
OH
D-glucose
H
HO
HO
O
OH
OH
"-D-glucofuranose (4)
H OH
HO
OH
!-D-glucopyranose (1)
H
a
HO
O
HO
CHO
OH
OH
OH
OH
a
HO
HO
HO
a
b
H
O
OH
OH
OH
"-D-glucopyranose (2)
b
at equilibrium in H2O: 1 ≈ 64%; 2 ≈ 36%; 3 + 4 < 1%
14 MUTAROTATION OF MONOSACCHARIDES:
THE CASE OF GLUCOSE
if one prepares an aqueous solu7on of either pure anomer of glucose, and one measures the specific op7cal rota7on of the solu7on over 7me, one observes that the rota7on of a solu7on of pure α-­‐anomer, ini7ally equal to +112°, drops to a final value of ca. +53°, while that of a solu7on of pure β-­‐anomer, ini7ally equal to +19°, increases to a final value of ca. +53°. H
H
OH
OH
+]
H
[
H
O
OH
HO
HO
HO
OH
O
HO
HO H
HO H
H
H
H
H
internal
"-D-glucopyranose
rotation
m.p. 150 °C
[!]D = + 19°
H
H
H
HO
HO
H
HO H
OH
OH
H
O
[ H+ ]
H
H
HO
HO
H
HO H
OH
O
H
OH
!-D-glucopyranose
m.p. 146 °C
[!]D = + 112°
This phenomenon is termed mutarota'on (="rota7on change") and it is due to equilibra7on of the anomers. At equilibrium, the solu7on contains a mixture of ca. 64% of β-­‐anomer (all equatorial, more stable) and ca. 36% of α-­‐anomer: (0.64 x 19°) + (0.36 x 112°) = 12.2° + 40.3° = +52.5° 15 CHEMICAL REACTIVITY OF CARBOHYDRATES
carbohydrates contain both OH and C=O groups ( oZen “masked” as hemiacetals); therefore, their reac7vity will parallel that of alcohols, hemiacetals, and C=O compounds: aldehyde
hemiacetal
H
HO
alcohols
O
HO
OH
OH
OH
!- or "-glucopyranose
H
HO
alcohols
OH
HO
O
OH
OH
open form of glucose
16 FORMATION OF GLYCOSIDES OF MONOSACCHARIDES
much like a hemiacetal will react with an alcohol under acidic condi7ons to form an acetal, so a monosaccharide will react under the same condi7ons to form an acetal termed a glycoside (riboside, glucoside, ….) HO
O
OH
CH3OH
HCl
– H2O
HO OH
!- or "-D-ribofuranose
HO
HO
HO
HO
H
O
HO OH
CH3OH
OH
HCl
– H2O
HO
OCH3
H
OCH3
HO OH
OH
O
H
HO
HO
O
+
!-methyl-D-ribofuranoside
OH
O
!- or "-D-glucopyranose
HO
OCH3
!-methyl-D-glucopyranoside
"-methyl-D-ribofuranoside
+
OH
O
OCH3
HO
HO
HO
H
"-methyl-D-glucopyranoside
note: the mechanism of these reac.ons is analogous to that seen earlier for simpler hemiacetals 17 HYDROLYSIS OF GLYCOSIDES IN AQUEOUS ACID
much like an acetal undergoes hydrolysis in aqueous acid, so a glycoside can be hydrolyzed back to a “free” sugar under aqueous acidic condi7ons OH
O
HO
HO
HO
aqueous
OCH3
!- or "-methyl-D-glucopyranoside
HCl
OH
O
HO
HO
HO
OH
!- and "-D-glucopyranoses
note: the mechanism of this reac.on is analogous to that seen earlier for simpler acetals 18 REDUCING AND NON-REDUCING SUGARS:
THE TOLLENS TEST
OH
O
HO
HO
HO
OH
!- or "-D-glucopyranose
hemiacetal:
reducing sugar
HO
HO
OH
OH
CHO
HO
free aldehyde
Ag(NH3)2 NO3
aq. NH3
(basic pH)
no hemiacetal:
nonreducing sugar OH
OH
O
OH
HO
HO
HO
HO
CHO
OCH
HO
3
HO
free aldehyde
!- or "-methyl-D-glucopyranoside
OH
OH
O
HO
HO
HO
+
O
ammonium
carboxylate
Ag0
metallic
silver
("mirror")
Ag(NH3)2 NO3
no reaction
aq. NH3
(basic pH)
reminder: an acetal is stable in the presence of bases, even strong ones like carbanions note: the mechanism of the Tollens reac.on is complex and will not be discussed in CHEM 203 importance of the Tollens test in the structural elucida7on of natually occurring carbohydrates 19 REDOX CHEMISTRY OF ALDOSES
• Oxida7on to aldonic or aldaric acids CHO
COOH
H
OH
H
OH
HNO3
H
HO
H
HO
H
OH
H
OH
H2O
H
OH
H
OH
OH
COOH
D-glucaric acid:
D-glucose
an aldaric acid
• Reduc7ons to alditols OH
O
HO
HO
HO
OH
!- or "-D-glucopyranose
HO
HO
OH
OH
CHO
HO
free aldehyde
Br2
H2O
H
HO
H
H
COOH
OH
H
OH
OH
OH
D-gluconic
acid:
an aldonic acid
H
HO
H
H
CHO
OH
H
OH
OH
OH
OH
H
OH
NaBH4
H
HO
H
OH
H
OH
OH
D-glucitol, a.k.a. D-sorbtol
(noncaloric sweetener)
20 REDUCTION OF KETOSES: FORMATION OF
DIASTEREOMERIC ALDITOLS
HO
O
OH
OH
HO
OH
OH OH
OH
HO
H
H
O
HO
HO
!- or "-D-fructofuranose
NaBH4
free ketone
H
HO
H
H
OH
OH
H
OH
OH
OH
D-glucitol
(D-sorbtol)
HO
HO
H
H
OH
O
H
OH
OH
OH
OH
H
H
OH
OH
OH
D-mannitol
21 FORMATION OF ETHERS BY WILLIAMSON REACTION
• Reducing sugars are generally poor substrates for the Williamson reac7on and must first be converted into glycosides: NaH, CH3I; or
OCH3
OH
OH
NaH,
(CH
O)
SO
O
CH
OH
(e.g.)
3 2
4
3
O
O
H3CO
HO
HO
H3CO
HO
HO
or NaOH, (CH3O)2SO4
cat.
HCl
OCH3
H3CO
OH
OCH3
HO
HO
!- or "-methyl-D-glucopyranoside
!- or "-D-glucopyranose
• Mild modifica7on of the Williamson reac7on: OH
O
HO
HO
HO
OH
Ag2O, CH3I
H3CO
H3CO
H3CO
OCH3
O
OCH3
!- or "-D-glucopyranose
22 POLYSACCHARIDES OR COMPLEX SUGARS
• Polysaccharides or complex sugars are polymers of monosaccharides arising through glycosyla7on of a monosaccharide with another monosaccharide • Disaccharides, trisaccharides, … oligosaccharides (“a few” saccharides, typically 2-­‐10 saccharide units), polysaccharides (more than ≈ 10 saccharide units) • Important disaccharides: sucrose, lactose, maltose: OH
O
HO
HO
HO
HO
HO
OH
!-D-glucopyranose
HO
OH
O
glycosylation
HO
HO
OH O
O
OH
OH
HO
OH
O
"-D-fructofuranose
no hemiacetals:
non-reducing
OH
HO
sucrose (table sugar):
a disaccharide
23 IMPORTANT DISACCHARIDES: LACTOSE & MALTOSE
OH
O
OH
HO
HO
HO
OH
O
HO
HO
HO
!-D-glucopyranose
glycosylation
HO
HO
HO
OH
HO
HO
HO
OH
!-D-glucopyranose
OH
O
HO
HO
HO
OH
!- or "-D-glucopyranose
OH
O
OH
HO
lactose (found in milk):
a disaccharide
"- or !-D-glucopyranose
OH
O
OH
O
O
HO
hemiacetal:
reducing
glycosylation
OH
O
HO
HO
HO
OH
O
O
HO
maltose:
a disaccharide
hemiacetal:
reducing
HO
OH
24 A TRISACCHARIDE: RAFFINOSE
OH
galactose
HO
HO
glucose
sucrose
HO
HO
HO
fructose
OH
O
O
O
HO
OH O
O
no hemiacetals:
non-reducing
OH
HO
• abundant in beans, broccoli, cabbage ,… • indiges7ble to humans • readily fermented by microorganism colonizing the human intes7ne yes, raffinose is the culprit 25 KEY POLYSACCHARIDES: AMYLOSE AND CELLULOSE
OH
O
O
HO
HO
OH
O
O
HO
HO
OH
O
O
HO
HO
amylose: a major
component of starch
OH
O
O
HO
HO
OH
O
O
HO
O
HO
HO
HO
cellulose: key structural material in
plants (cotton ≈ 90%; wood ≈ 50%)
OH
O
O
HO
HO
OH
O
O
HO
HO
OH
O
O
HO
HO
O
n
OH
O
O
HO
OH
O
O
HO
n
26 ACIDIC HYDROLYSIS OF POLYSACCHARIDES
OH
O
HO
HO
HO
OH O
O
HO
sucrose
HO
HO
dil. aq.
OH
lactose
HO
OH
O
O
HO
OH
O
+
HO
OH
OH
OH
HO
dil. aq.
2
H2SO4
OH
O
D-glucopyranose
HO
HO
HO
OH
HO
H2SO4
HO
OH
O
D-fructofuranose
OH
O
HO
HO
HO
OH
D-glucopyranose
a polysaccharide can be hydrolyzed to simpler carbohydrates (ul7mately, to free monosaccharides) with dilute aqueous acid (hydrolysis of the acetal func7ons), while a monosaccharide cannot be converted to simpler sugars under the same condi7ons 27 FORMATION OF GLYCOSYLAMINES
• a free monosaccharide reacts with aqueous ammonia to yield a glycosylamine OH
O
HO
HO
aq.
OH NH3
HO
OH
OH
H
HO
HO
HO
Schiff
base
form.
O
OH
OH
H
HO
HO
HO
HO
HO
HO
NH
D-glucopyranose
likewise:
OH
O
NH2
glucosylamine:
a glycosylamine
O
HO
OH
aq.
O
HO
NH2
NH3
HO
OH
D-ribofuranose
HO
OH
ribosylamine: a glycosylamine
• relevance of glycosylamines to nucleic acid chemistry . . . 28 PYRIMIDINE AND PURINE: HETEROCYCLES OF LIFE
O
NH
N
N
pyrimidine
NH2
O
N
H
NH
N
H
O
uracil
N
N
H
O
thymine
cytosine
NH2
N
N
H
N
N
purine
N
N
H
N
N
adenine
O
O
N
N
H
NH
N
NH2
guanine
29 RIBONUCLEOTIDES: COMPONENTS OF RNA
NH
NH
N
H
O
HO
O
N
HO OH
N
NH2
N
uridine
HO
N
O
N
H
uracil
O
HO OH
adenine
HO
O
cytosine
O
N
N
adenosine
N
O
N
O
cytidine
HO OH
N
O
N
N
N
N
NH2
NH2
N
H
NH2
O
O
N
H
HO
NH
N
guanine
NH2
O
N
HO OH
NH
N
NH2
guanosine
30 2-DESOXYRIBONUCLEOTIDES: COMPONENTS OF DNA
O
O
NH
NH
N
H
HO
O
O
thymine
HO
NH2
N
HO
O
N
2-desoxythymidine
O
N
N
HO
O
HO
O
NH2
N
N
N
2-desoxyadenosine
HO
N
HO
O
O
2-desoxycytidine
HO
N
NH
N
NH2
2-desoxyguanosine
31