• 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 nucleic acids, glycoproteins antigens, immune responses materials & fibers cancer cell markers extracellular support matrices energy storage & generation 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 HOCH2–(CHOH)x–(CO)–(CHOH)y–CH2OH
an aldose 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 HOCH2–(CHOH)x–(CO)–(CHOH)y–CH2OH
an aldose 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 OH CHO H OH O H OH HO H HO H H OH H OH H OH H OH H OH H OH OH OH OH ribose glucose 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 CHO H OH enantiomers HO H OH HO
D-(R)-(+)-glyceraldehyde L-(S)-(–)-glyceraldehyde (OH on the right) (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 OH glyceraldehyde CHO (aldotriose) CHO H OH HO H H OH H OH OH (aldotetroses) OH erythrose threose CHO CHO CHO CHO H OH HO H H OH HO H H OH H OH (aldopentoses) HO H HO H H OH H OH H OH H OH OH OH OH OH ribose arabinose xylose lyxose
(aldohexoses)
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 OH OH OH OH OH OH OH OH
allose altrose glucose mannose gulose idose galactose talose
06 D- AND L-MONOSACCHARIDES
enantiomeric compounds!
CHO CHO H OH HO H OH HO D-(R)-(+)-glyceraldehyde L-(S)-(–)-glyceraldehyde (OH on the right) (OH on the left)
CHO CHO CHO CHO CHO H OH HO H 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 HO H OH H OH HO H HO OH HO L-erythrose D-erythrose OH HO D-ribose L-ribose D-glucose 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 OH R O R O
OH 5- or 6-membered ring
08 HEMIACETAL FORMS OF D-RIBOSE AND D-GLUCOSE
wavy line means that either Ribose (building block of RNA): configuration is possible
CHO H H OH O OH H OH HO CHO HO H OH H OH HO OH HO OH OH aldehyde (carbonyl) common hemiacetal form of D-ribose (preferred) Fischer projection form of D-ribose of D-ribose Glucose: CHO H H H OH OH O OH HO CHO HO HO H H OH HO OH HO OH H OH OH OH OH aldehyde (carbonyl) common hemiacetal form of D-glucose (preferred) Fischer projection form of D-glucose of D-glucose 09 FURANOSE AND PYRANOSE FORMS OF MONOSACCHARIDES
O O O O
furan tetrahydrofuran pyran tetrahydropyran
H H O OH O OH HO furanose form HO pyranose form of D-ribose of D-glucose ("D-ribofuranose") HO OH ("D-glucopyranose") HO OH 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 H H H O OH O OH O OH O OH HO HO HO HO HO OH HO OH HO OH HO OH OH OH -anomer of !-anomer of "-anomer of !-anomer of " D-glucopyranose D-ribofuranose D-ribofuranose D-glucopyranose ( -D-glucopyranose) (!-D-ribofuranose) ("-D-ribofuranose) (!-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 OH H H OH HO O OH O H HO HO HO H H HO OH H HO OH HO H O H H OH H OH HO all equatorial: A-value of OH < 1.0 kcal/mol "-D-glucopyranose favored A-value of CH2OH ≈ 2 kcal/mol H H OH O OH H OH HO HO O H H HO H HO H H HO OH H HO H O OH OH H HO OH OH !-D-glucopyranose all but 1 OH equatorial: favored under appropriate condi ons, it is possible to obtain pure α-D-glucopyranose or pure β-D-glucopyranose (crystalliza on). These two anomeric forms of glucopyranose, being diastereomeric, differ in solubility, mel ng point (146 °C for the α-anomer, 150 °C for the 25 β-anomer), and op cal rota on ([a]D = +112° for the α-anomer, + 19° for the β-anomer).
12 INTERCONVERSION OF PYRANOSE AND FURANOSE FORMS AND OF α- and β-ANOMERS: RIBOSE
H O OH CHO O OH H OH HO HO OH b H OH a HO OH OH H OH OH !-D-ribofuranose !-D-ribopyranose D-ribose H O OH b a O OH HO H OH a HO OH HO HO OH OH CHO HO "-D-ribofuranose "-D-ribopyranose 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
CHO H HO O OH H OH HO H OH O HO H HO HO OH b H OH a OH HO OH H OH OH !-D-glucopyranose (1) !-D-glucofuranose (3) D-glucose H HO O OH b a HO H O OH a HO H OH HO OH HO CHO OH HO OH HO OH "-D-glucopyranose (2) "-D-glucofuranose (4) OH 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 solu on of either pure anomer of glucose, and one measures the specific op cal rota on of the solu on over me, one observes that the rota on of a solu on of pure α-anomer, ini ally equal to +112°, drops to a final value of ca. +53°, while that of a solu on of pure β-anomer, ini ally equal to +19°, increases to a final value of ca. +53°.
H OH H OH H H OH H [ H+ ] H H OH [ H+ ] H O OH O HO HO HO OH HO HO OH HO O HO H HO H HO H HO H H HO H HO H OH H H H H O H internal "-D-glucopyranose -D-glucopyranose rotation ! m.p. 150 °C m.p. 146 °C [!]D = + 19° [!]D = + 112°
This phenomenon is termed mutarota on (="rota on change") and it is due to equilibra on of the anomers. At equilibrium, the solu on 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 ( o en “masked” as hemiacetals); therefore, their reac vity will parallel that of alcohols, hemiacetals, and C=O compounds:
hemiacetal aldehyde H H O OH OH O HO HO
HO OH HO OH alcohols alcohols OH OH
!- or "-glucopyranose open form of glucose
16 FORMATION OF GLYCOSIDES OF MONOSACCHARIDES
much like a hemiacetal will react with an alcohol under acidic condi ons to form an acetal, so a monosaccharide will react under the same condi ons to form an acetal termed a glycoside (riboside, glucoside, ….)
HO HO HO CH OH O 3 O H OCH3 OH + O HCl OCH3 H HO OH – H2O HO OH HO OH
!- or "-D-ribofuranose !-methyl-D-ribofuranoside "-methyl-D-ribofuranoside
OH OH OH CH3OH O O HO O HO + HO HO H HO OCH HO HCl 3 HO OH HO HO – H2O OCH3 H !- or "-D-glucopyranose !-methyl-D-glucopyranoside "-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 condi ons
OH OH O aqueous HO HO O HO HCl HO HO OCH3 HO OH
!- or "-methyl-D-glucopyranoside !- 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
hemiacetal: OH OH reducing sugar OH Ag(NH ) NO HO OH O OH 3 2 3 0 HO HO HO O + Ag HO HO CHO aq. NH HO HO OH 3 O HO (basic pH) metallic free aldehyde ammonium silver !- or "-D-glucopyranose carboxylate ("mirror") no hemiacetal: OH nonreducing sugar OH Ag(NH ) NO HO O OH 3 2 3 HO no reaction HO HO aq. NH HO OCH CHO 3 3 HO (basic pH) !- or "-methyl-D-glucopyranoside free aldehyde 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 elucida on of natually occurring carbohydrates
19 REDOX CHEMISTRY OF ALDOSES
• Oxida on to aldonic or aldaric acids
COOH CHO COOH H OH H OH H OH HNO3 Br2 HO H HO H HO H
H OH H2O H OH H2O H OH H OH H OH H OH OH OH COOH D-glucaric acid: D-glucose D-gluconic acid: an aldaric acid an aldonic acid
• Reduc ons to alditols
CHO OH OH OH H OH H OH O NaBH HO HO OH HO H 4 HO H HO HO CHO H OH H OH HO OH HO H OH H OH free aldehyde !- or "-D-glucopyranose OH OH D-glucitol, a.k.a. D-sorbtol (noncaloric sweetener)
20 REDUCTION OF KETOSES: FORMATION OF DIASTEREOMERIC ALDITOLS
OH HO HO OH OH OH O O OHOH HO H OH O H OH HO HO H OH !- or "-D-fructofuranose free ketone OH
OH OH H OH HO H NaBH4 HO H HO H H OH H OH H OH H OH OH OH
D-glucitol D-mannitol (D-sorbtol)
21 FORMATION OF ETHERS BY WILLIAMSON REACTION
• Reducing sugars are generally poor substrates for the Williamson reac on and must first be converted into glycosides:
NaH, CH I; or OH OH 3 OCH3 CH OH (e.g.) NaH, (CH3O)2SO4 O HO O 3 HO O H3CO HO HO H3CO cat. HCl or NaOH, (CH3O)2SO4 H CO OCH HO OH HO OCH3 3 3 !- or "-D-glucopyranose !- or "-methyl-D-glucopyranoside
• Mild modifica on of the Williamson reac on:
OH OCH3 O Ag O, CH I O HO 2 3 H3CO HO H3CO HO OH H3CO OCH3 !- or "-D-glucopyranose
22 POLYSACCHARIDES OR COMPLEX SUGARS
• Polysaccharides or complex sugars are polymers of monosaccharides arising through glycosyla on 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 OH HO HO O HO OH HO !-D-glucopyranose glycosylation HO HO OH no hemiacetals: O non-reducing O HO OH OH O OH OH HO HO sucrose (table sugar): -D-fructofuranose " a disaccharide
23 IMPORTANT DISACCHARIDES: LACTOSE & MALTOSE
hemiacetal: reducing OH OH glycosylation HO O OH HO O OH HO OH HO O HO O O HO HO HO HO HO OH HO OH !-D-glucopyranose lactose (found in milk): "- or !-D-glucopyranose a disaccharide
OH OH hemiacetal: glycosylation reducing HO O OH HO O O HO HO HO OH HO HO HO OH O O HO OH !-D-glucopyranose HO !- or "-D-glucopyranose HO OH maltose: a disaccharide
24 A TRISACCHARIDE: RAFFINOSE
OH OH galactose O HO HO O HO O glucose no hemiacetals: HO non-reducing HO sucrose HO OH O O fructose OH HO
• abundant in beans, broccoli, cabbage ,…
• indiges ble to humans
• readily fermented by microorganism colonizing the human intes ne
yes, raffinose is the culprit
25 KEY POLYSACCHARIDES: AMYLOSE AND CELLULOSE
OH O O HO OH HO O O HO OH HO O O HO OH HO O O amylose: a major HO component of starch HO O n
OH O O OH HO O O OH HO HO O O OH HO HO O O OH HO HO O O OH HO HO O O cellulose: key structural material in HO HO O plants (cotton ≈ 90%; wood ≈ 50%) HO n
26 ACIDIC HYDROLYSIS OF POLYSACCHARIDES
OH HO O HO OH HO OH HO O O OH HO OH O dil. aq. HO O HO + OH OH H2SO4 HO sucrose OH HO D-glucopyranose HO D-fructofuranose OH OH O HO O OH dil. aq. HO O 2 HO HO O OH HO HO H2SO4 HO lactose OH HO D-glucopyranose a polysaccharide can be hydrolyzed to simpler carbohydrates (ul mately, to free monosaccharides) with dilute aqueous acid (hydrolysis of the acetal func ons), while a monosaccharide cannot be converted to simpler sugars under the same condi ons
27 FORMATION OF GLYCOSYLAMINES
• a free monosaccharide reacts with aqueous ammonia to yield a glycosylamine
OH OH Schiff OH OH aq. OH base OH HO O HO HO HO O HO HO H HO H NH form. HO OH 3 HO HO NH2 HO O NH HO D-glucopyranose glucosylamine: a glycosylamine
O aq. O HO OH HO NH2 likewise: NH3 HO OH HO OH
D-ribofuranose ribosylamine: a glycosylamine
• relevance of glycosylamines to nucleic acid chemistry . . .
28 PYRIMIDINE AND PURINE: HETEROCYCLES OF LIFE
O O NH2
N NH NH N
N N O N O N O H H H pyrimidine uracil thymine cytosine
NH2 O N N N N N NH
N N N N H H N H N NH2 purine adenine guanine
29 RIBONUCLEOTIDES: COMPONENTS OF RNA
NH O O 2 N NH2 N NH NH N HO HO N N N O O N N O O H N N H adenosine uracil HO OH HO OH uridine adenine O NH NH 2 N 2 O NH N HO N N N HO NH O N NH2 N O N O O N H N NH2 cytidine H HO OH guanosine cytosine guanine HO OH
30 2-DESOXYRIBONUCLEOTIDES: COMPONENTS OF DNA
O O
NH NH HO N O N O O H thymine HO 2-desoxythymidine
NH2 O NH2 N N N N NH HO HO N N HO N O N O O N NH2 O
HO 2-desoxyadenosine HO 2-desoxyguanosine HO 2-desoxycytidine
31