Carbohydrates
Carbohydrates are compounds that have the general formula CnH2nOn
Because CnH2nOn can also be written Cn(H2O)n, they appear to be “hydrates of carbon”
Carbohydrates are also called “sugars” or “saccharides”
Carbohydrates can be either aldoses (ald is for aldehyde and ose means a carbohydrate) or ketoses (ket is for ketone)
O
OH OH
OHC
CH2OH
OH OH
An Aldose
(D-Glucose)
HOH2C
OH
CH2OH
OH OH
A Ketose
(D-Fructose)
Carbohydrates
Due to the multiple chiral centers along a linear carbon chain for carbohydrates, Emil Fischer developed the “Fischer Projection” in order to represent these compounds
Remember how to draw a Fischer projection:
1)  View the linear carbon chain along the vertical axis (always place the more oxidized carbon [aldehyde in an aldose] towards the top)
2) The horizontal lines are coming out of the page toward the viewer
3) Will need to change the viewpoint for each carbon so the horizontal substituents are
always pointing towards the viewer
OH OH
OHC
CH2OH
OH OH
Emil Fischer
(1852-1919)
=
H
HO
H
H
CHO
OH
H
OH
OH
CH2OH
Carbohydrates
The aldoses are thus all related by having an aldehyde group at one end, a primary alcohol
group at the other end, and the two ends connected by a series of H-C-OH groups
CHO
H
OH
CH2OH
CHO
H
OH
H
OH
CH2OH
Aldotriose
Aldotetrose
D-glyceraldehyde
D-erythose
CHO
H
OH
H
OH
H
OH
CH2OH
Aldopentose
D-ribose
H
H
H
H
CHO
OH
OH
OH
OH
CH2OH
Aldohexose
D-allose
HO
HO
HO
HO
CHO
H
H
H
H
CH2OH
Aldohexose
L-allose
The D-aldoses are named according to glyceraldehyde, the D refers to the configurational carbon (H-C-OH group next to primary alcohol), if OH is to the right in Fischer it is called D (after dextrorotatory – “to the right” in Latin), if OH is to the left in Fischer it is called L (after levorotatory – “to the left” in Latin)
Naturally occurring sugar molecules have the D configuration
Reactions of Carbohydrates
Carbohydrates react similar to other aldehydes and carbonyl groups observed earlier
Due to the presence of the other alcohol groups in a carbohydrate, aldoses readily form acetal and hemiacetal linkages when the aldehyde reacts
H
O
HC
H
OH
H
HO
H
OH
H
OH
CH2OH
H
HOHO
O
HO
H
H
OH
OH
H
α-D-glucofuranose
H OH
H
H
OH
O
HOHO
H
HO
H
H
OH
H
β-D-glucofuranose
O
tetrahydrofuran
H OH
HO
HO
HO
H
H
OH
OH
α-D-glucopyranose
O
HO
HO
HO
H
H
OH
H
OH
β-D-glucopyranose
tetrahydropyran
The hemiacetal formation thus forms ring structures, either 5-membered (furanoses) or 6-membered (pyranoses) rings are favored
When the aldehyde reacts, a new chiral center is formed, these isomers are called “anomers” and designated as the α- or β-anomer
Reactions of Carbohydrates
The majority of the sugar molecules in solution are in the cyclic hemiacetal form, although in equilibrium with the aldehyde open form
H
OH
O
HOHO
H
HO
H
H
OH
H
H
HO
H
H
CHO
OH
H
OH
OH
CH2OH
H OH
HO
HO
HO
H
H
OH
H
OH
Aldohexose Pyranose form Furanose form The ratio of the pyranose and furanose
forms depends upon the aldohexose
being considered
Allose 92 8 altrose 70 30 glucose ~100 <1 mannose ~100 <1 gulose 97 3 idose 75 25 galactose 93 7 talose 69 31 Reactions of Carbohydrates
The 1H NMR of glucose also indicates the presence of the two anomers of the predominant pyranose form
H OH
HO
HO
HO
β
H OH
H
H
H
OH
OH
HO
HO
HO
H
H
α-D-glucopyranose
OH
H
OH
α
β-D-glucopyranose
Aldohexose α-­‐Pyranose β-­‐Pyranose α-­‐Furanose β-­‐Furanose Allose 16 76 3 5 Altrose 27 43 17 13 Glucose 36 64 <1 <1 Mannose 66 34 <1 <1 Gulose 16 81 <1 3 Idose 39 36 11 14 Galactose 29 64 3 4 Talose 37 32 17 14 Haworth Form
Another representation of carbohydrates in the hemiacetal form is to draw a “Haworth form”
In the Haworth form, the ring is drawn in a planar perspective and the substituents are drawn either above or below the plane of the ring
The Haworth form does not indicate the axial and equatorial relationship as the chair
conformation does, but it is a convenient representation for the pyranose and furanose rings
H
HO
H
H
CHO
OH
H
OH
OH
CH2OH
Fischer projection
D-glucose
H OH
HO
HO
HO
H
H
OH
H
OH
Chair conformation
β-D-glucopyranose
CH2OH
OOH
OH
OH
OH
CH2OH
O
OH
OH
OH
OH
Haworth form
Haworth form
β-D-glucopyranose
α-D-glucopyranose
Reactions of Carbohydrates
Carbohydrates can undergo a variety of reactions similar to any other carbonyl compound
The Kiliani-Fischer synthesis allows the conversion of a carbohydrate into another
carbohydrate with one additional carbon, a so-called chain lengthening procedure
O
H
HO
H
C
H
OH
NaCN
H
OH
CH2OH
D-Xylose
N
C
H C OH
H
OH
H
HO
H
OH
CH2OH
N
HN
H
C
C
H C OH
HO C H
H
OH
H
OH
H2/Pd
H
HO
H
HO
H
H
OH
OH "poisoned"
CH2OH
CH2OH
epimers
Reaction of aldehyde with cyanide creates a cyanohydrin
But two stereoisomers are created with new chiral center
Reduction of nitrile with poisoned catalyst creates imine
Which upon hydrolysis creates two new sugar compounds
with one additional carbon (aldopentose becomes an aldohexose)
HN
H
C
HO C H
H
OH
H
HO
H
OH
CH2OH
H+, H2O
H
C
H C OH
H
OH
H
HO
H
OH
CH2OH
H
C
HO C H
H
OH
H
HO
H
OH
CH2OH
D-Gulose
D-Idose
O
O
Reactions of Carbohydrates
Carbohydrates can also have a chain shortening procedure through a “Ruff degradation”
H
HO
H
H
CHO
OH
H
OH
OH
CH2OH
D-Glucose
O
1) Br2, H2O
2) Ca(OH)2
H
HO
H
H
C
Ca
O
OH
H
OH
OH
CH2OH
1) Fe2(SO4)3,
H2O
2) H2O2 (30%)
CHO
H
HO
H
OH
H
OH
CH2OH
D-Arabinose
First the carbohydrate is oxidized to a carboxylic acid (Br2 is a selective oxidant) and the calcium salt is obtained by reaction with calcium hydroxide
The calcium salt is then decarboxylated with ferric ion (need to use weak hydrogen peroxide to stop at aldehyde stage)
Thus overall a aldohexose is converted into an aldopentose, maintaining the chirality at all remaining chiral centers
Reactions of Carbohydrates
In solution, carbohydrates are in the cyclic hemiacetal form the majority of the time
H OH
HO O
HO
HO
H
H
H
HO
HO
H
H
H
OH
α-D-mannopyranose
CHO
H
H
OH
OH
CH2OH
H OH
HO O
HO
HO
H
OH
H
H
H
β-D-mannopyranose
The cyclic form equilibrates, however, with the open chain aldehyde form
When the open form recloses to the hemiacetal, it could create two anomers (α and β)
In solution, therefore, a carbohydrate equilibrates between the α and β forms (called mutarotation)
Each carbohydrate has its own ratio of these forms at equilibrium
Aldohexose α-­‐Pyranose β-­‐Pyranose α-­‐Furanose β-­‐Furanose Mannose 66 34 <1 <1 Reactions of Carbohydrates
While in neutral solution carbohydrates equilibrate between the two anomers, when treated with base a carbohydrate equilibrates into both an epimer (by inversion of the
stereocenter adjacent to the aldehyde) and by conversion of the aldose to a ketose
Squiggly line means
both anomers
H OH
HO
Ca(OH)2
HO
H
H
OH
OH
OH
D-Allose
Chirality has
changed
H OH
HO
HO O
H
H
OH
H
Ca(OH)2
OH
D-Altrose
CH2OH
O
H
OH
H
OH
H
OH
CH2OH
D-Psicose
Epimerization occurs through enolate formation at α-position
H
H
H
H
CHO
OH
OH Ca(OH)2
OH
OH
CH2OH
O
H
OH
H
OH
H
OH
H
OH
CH2OH
CH2OH
O
H
OH
H
OH
H
OH
CH2OH
When enolate is
protonated at α position,
two epimers are obtained
When enolate equilibrates
with enol, a ketose is
obtained
Reactions of Carbohydrates
Any carbohydrate that contains a hemiacetal can equilibrate to the aldose form
H OH
HO
H
H
H
H
HO
H
H
OH
OH
OH
CHO
OH
OH
OH
OH
CH2OH
In the presence of sodium borohydride, the aldehyde can be reduced to a primary alcohol
(this is why the aldohexoses are called “reducing sugars”, the aldehyde is reduced to alcohol)
H
H
H
H
CHO
OH
OH
OH
OH
CH2OH
NaBH4
H
H
H
H
CH2OH
OH
OH
OH
OH
CH2OH
Notice that the carbohydrate after reduction has two terminal primary alcohol groups,
depending upon the chirality of the initial carbohydrate a meso compound can be obtained
Reactions of Carbohydrates
Carbohydrate can also be oxidized, but due to the presence of an aldehyde in aldoses and a multitude of alcohol groups (primary and secondary), different oxidizing conditions can selectively oxidize different parts of the carbohydrate
Bromine in water selectively oxidizes only the aldehyde group into a carboxylic acid
(the other alcohols in the molecule are unaffected)
H
H
H
H
CHO
OH
OH
OH
OH
CH2OH
D-Allose
Br2
H2 O
H
H
H
H
CO2H
OH
OH
OH
OH
CH2OH
D-Allonic acid
The two ends of the allonic acid are different, thus allonic acid is a chiral molecule
Reactions of Carbohydrates
If stronger oxidizing conditions are used, both the aldehyde and the primary alcohol can be
oxidized to carboxylic acids (typically reagent is nitric acid) [called aldaric acids]
H
H
H
H
CHO
OH
OH
OH
OH
CH2OH
H
H
H
H
HNO3
CO2H
OH
OH
OH
OH
CO2H
Similar to the reduction of carbohydrates with NaBH4, this reaction also creates two identical
end groups (both carboxylic acids) which can result in meso compounds
H
HO
H
H
CHO
OH
H
OH
OH
CH2OH
D-Glucose
HNO3
H
HO
H
H
CO2H
OH
H
OH
OH
CO2H
Glucaric acid
chiral
H
HO
HO
H
CHO
OH
H
H
OH
CH2OH
D-Galactose
HNO3
H
HO
HO
H
CO2H
OH
H
H
OH
CO2H
Galactaric acid
achiral
Reactions of Carbohydrates
Another oxidation observed earlier is when periodate reacts with vicinal diols
O
O I O
O
HO
O
O I O
O
O
OH
O
O
I
O
O
CH2
O
CH2
Vicinal primary alcohols are thus oxidized to formaldehyde
O
H2O
OH
HO
HO
H
O
O I O
O
OH
O
HO
H
O
CH2
H
Aldehydes hydrate to a geminal diol which can be oxidized to formic acid
OH
HO
OH
O
O I O
O
O
CH2
O
OH
O
O I O
O
O
HO
H
O
CH2
Secondary alcohols of a carbohydrate will be also be oxidized twice to formic acid
Reactions of Carbohydrates
Due to the variety of carbonyl or alcohol groups on adjacent carbons of carbohydrates,
periodate oxidation of sugars was historically convenient to determine structure
H
HO
H
H
CHO
OH
H
OH
OH
CH2OH
O
O I O
O
HCO2H
HCO2H
HCO2H
HCO2H
HCO2H
H2 C O
D-Glucose
H
HO
H
H
CH2OH
OH
H
OH
OH
CH2OH
Sorbitol
CH2OH
O
H
HO
H
OH
H
OH
CH2OH
O
O I O
O
H2 C O
O C O
HCO2H
HCO2H
HCO2H
H2 C O
D-Fructose
O
O I O
O
H2 C O
HCO2H
HCO2H
HCO2H
HCO2H
H2 C O
Oxidation of glucose, or any aldohexose, produces 5
equiv. of formic acid and one equiv. of formaldehyde
Oxidation of sorbitol produces instead 4 equiv. of
formic acid and 2 equiv. of formaldehyde
Oxidation of fructose, or any ketohexose, produces 3
equiv. of formic acid, 2 equiv. of formaldehyde and 1
equiv. of carbon dioxide
The ratio of products thus determines if structure was
an aldohexose, reduced sugar, or ketohexose
Reactions of Carbohydrates
The hemiacetal form of carbohydrates equilibrate with the open form and thus reactions of
these carbohydrates can be written as occurring through the open form
While hemiacetals equilibrate with the open form, acetals are more stable and do not equilibrate
H OH
H OH
HO
HO
HO
H
H
HCl
H
OH
OH
HO
HO
HO
H
H
H OH
H OH
H
OH
OH2
HO
H O CH3OH
HO
HO
H OH
HO
HO
H
H
H
H
OH
OCH3
Under catalytic acid conditions, only the anomeric carbon will react due to the resonance
stabilized cation after loss of water to allow formation of glycoside (a stable acetal)
H OH
HO
HO
HO
H
H
H
OH
OH
CH3OH
HCl
H3O+, !
H OH
HO
HO
HO
H
H
Will obtain both α
H and β anomers
OH
OCH3
As seen with acetals, this reaction is reversible under acidic aqueous conditions
Reactions of Carbohydrates
The stable acetal forms allowed chemists to use the periodate oxidation procedure to also
determine the ring size of the closed form (furanose versus pyranose)
O
O I O
O
H OH
HO
HO
HO
H
H
OH
OH
H3O+, !
O
OHC
OHC
H
OH
OCH3
HCO2H
H
OH
OHC
OHC CHO
OCH3
CH3OH
D-Glucopyranoside
When the pyranoside ring structure is oxidized and then the acetal hydrolyzed, the products
obtained are formic acid, glyceraldehyde, glyoxal and methanol
H
H
O
O I O
O
O
HOHO
H
HO
H
OCH3
OH
H
CH3OH
H2 C O
OHC
O
OCH3
CHO CHO
H3O+, !
OHC
OH
CHO
CHO
CHO
D-Glucofuranoside
When the furanoside ring structure is oxidized, however, different products are obtained
Reactions of Carbohydrates
The aldehyde functionality present in the open form of a carbohydrate can undergo a variety of carbonyl reactions If the carbohydrate is reacted with phenyl hydrazine, a phenyl hydrazone is obtained
H OH
H
HO
H
H
HO
HO
HO
H
H
H
OH
OH
CHO
OH
H
OH
OH
CH2OH
H
H
HO
H
H
PhNHNH2
HN
N
Ph
OH
H
OH
OH
CH2OH
With excess phenyl hydrazine, however, the phenyl hydrazone reacts again to form an osazone
H
H
HO
H
H
HN
N
Ph
OH
H
OH
OH
CH2OH
H
PhNHNH2
HN
N
Ph
N
Ph
N
H H
HO
H
OH
H
OH
CH2OH
Reactions of Carbohydrates
The reaction involves the enamine in equilibrium with the imine also equilibrating with the
ketone at the C2 carbon position, which then reacts with the phenyl hydrazine
H
H
HO
H
H
HN
N
Ph
H
OH
H
OH
OH
CH2OH
Ph
HN
NH
Ph
HN
H
NH
H
O
PhNHNH2
H
HO
H
OH
-NH3
H
OH
-PhNH2
CH2OH
OH
H
HO
H
OH
H
OH
CH2OH
H
HN
N
Ph
N
Ph
N
H H
HO
H
OH
H
OH
CH2OH
Since both the C1 and C2 carbons react in an osazone, the chirality at the C2 position is lost
H
HO
H
H
CHO
OH
PhNHNH2
H
OH
OH
CH2OH
D-Glucose
H
HN
N
Ph
N
Ph
N
PhNHNH2
H H
HO
H
OH
H
OH
CH2OH
Osazone
HO
HO
H
H
CHO
H
H
OH
OH
CH2OH
D-Mannose
Reactions of Carbohydrates
While the hemiacetal form of a carbohydrate can be alkylated at the anomeric carbon under
catalytic conditions, the carbohydrate can be fully alkylated with excess alkyl halide
H OCH3
HO
H3CO
H3CO
H
H
CH3I
H
OCH3
OCH3
catalytic
HCl
H2O
H OCH3
HO
H3CO
H3CO
H
H
H
OCH3
OH
Ag2O
H OH
catalytic
HCl
HO
HO
HO
H
H
H
OH
OH
CH3OH
H OH
HO
HO
HO
H
H
H
OH
OCH3
A similar reaction can occur with acid chlorides or acid anhydrides
to form the fully acetylated version of carbohydrates
Due to the higher reactivity of the anomeric carbon, this position can
be selectively dealkylated under catalytic acid hydrolysis
Through a series of related reactions, various hydroxyl groups of the
carbohydrate can be protected selectively
Fischer Proof of Carbohydrate Chirality
In 1891 Fischer was able to prove the structure of each aldohexose sugar molecule
This was a stunning accomplishment as the concept of tetrahedral chirality of carbon was
only first proposed in 1876 by van’t Hoff and was still debated at that time
Using the tetrahedral chirality, Fischer could rationalize that there were 16 chiral versions of an aldohexose
Fischer also realized that these 16 stereoisomers were related as two sets of enantiomers (8 L-sugars and 8 D-sugars)
H
H
H
H
CHO
CHO
CHO
CHO
CHO
CHO
CHO
CHO
OH HO
OH HO
OH HO
OH HO
OH
OH HO
OH
OH HO
HO
HO
OH
HO
OH
OH
OH HO
HO
HO
OH
OH
OH
OH
OH
OH
OH
OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
While Fischer could rationalize that these are the 8 possible D-sugars, which structure corresponds to glucose (or any of the other sugars) is unknown
Fischer Proof of Carbohydrate Chirality
Fischer was able to correctly predict the absolute structure of each aldohexose by
rationalizing the chirality and symmetry upon reactions of the sugars
Experimental evidence used by Fischer to prove structure of glucose:
1)
Glucose
HNO3
Glucaric acid
1) !
2) reduce
“Gulose”
Glucaric acid is chiral
2)
Glucose and Mannose give same osazone
Arabinose
Fructose
1) Kiliani-Fischer
2) oxidize CHO
reduce
Gluconic and Mannonic acids
Glucitol and Mannitol
Mannitol and Mannonic acid are chiral
3)
Arabinose
Xylose
Kiliani-Fischer
Kiliani-Fischer
Glucose and Mannose
Gulose and Idose
Arabinose gives active Arabitol and Arabaric diacid
Xylose gives inactive Xylitol and Xylaric diacid
Fischer Proof of Carbohydrate Chirality
An aldotriose is the
shortest possible sugar
CHO
OH
OH
CH2OH
CHO
OH
OH
OH
CH2OH
CHO
OH
CH2OH
D-Glyceraldehyde
CHO
Kiliani-Fischer generates
two new aldotetroses
CHO
OH
CH2OH
CHO
OH
HO
OH
OH
CH2OH
HO
HO
OH
CH2OH
CHO
HO
HO
OH
CH2OH
CHO
CHO
CHO
CHO
CHO
CHO
CHO
CHO
OH HO
OH HO
OH HO
OH HO
OH
OH HO
OH
OH HO
HO
HO
HO
OH
OH
OH
OH HO
HO
HO
OH
OH
OH
OH
OH
OH
OH
OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
These will be all the D-sugars up to the aldohexoses
Which stereoisomer is naturally occurring glucose?
Fischer Proof of Carbohydrate Chirality
Fischer used the results of known reactions to deduce which steroisomer is glucose
Ultimately the stereochemistry of the aldohexoses was determined through symmetry:
1) Diacid oxidized form of glucose is chiral, Gulose differs by converting CHO and 1˚ OH
2) Mannose differs only at C2, plus diacid form of Mannose is chiral
3) Arabinose yields Glucose and Mannose, oxidized form of Arabinose is chiral
CHO
CHO
OH
HO
OH
OH
CH2OH
Arabinose
HO
OH
CH2OH
Xylose
CHO
CHO
CHO
CHO
CHO
CHO
CHO
CHO
OH HO
OH HO
OH HO
OH HO
OH
OH HO
OH
OH HO
HO
HO
HO
OH
OH
OH
OH HO
HO
HO
OH
OH
OH
OH
OH
OH
OH
OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
Glucose
Mannose
Gulose
Idose
Naming of Sugar Compounds
CHO
CHO
A few of the sugars are natural OH
HO
and have common names
OH
OH
Remaining names from Fischer
CH2OH
CH2OH
Erythrose
Greek for “red”
CHO
OH
OH
OH
CH2OH
Ribose
Transpose arabinose
Threose
Reverse “erth”
CHO
CHO
OH
HO
OH
OH
CH2OH
Arabinose
“Gum arabic”
HO
OH
CH2OH
Xylose
Greek for “wood”
CHO
HO
HO
OH
CH2OH
Lyxose
Reverse “xyl”
CHO
CHO
CHO
CHO
CHO
CHO
CHO
CHO
OH HO
OH HO
OH HO
OH HO
OH
OH HO
OH
OH HO
HO
HO
HO
OH
OH
OH
OH HO
HO
HO
OH
OH
OH
OH
OH
OH
OH
OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
CH2OH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
“alter”
“sweet wine”
“manna”
GLU - GUL
“Ibid–ID.”
“milk sugar”
LAT-TAL
Disaccharides
Disaccharides are a result of two monosaccharides (sugars) connected through an acetal bond
OH
OH
CHO
OH
OH
O
O
O
OH HO
HO
OH
OH
H+
H2 O
Lactose
(found in milk)
OH
HO
HO
HO
HO
OH
O
CH2OH
OH
O
OH
CH2OH
Sucrose
(refined from cane sugar)
HO
OH
CH2OH
OH
OH
CH2OH
D-Galactose
D-Glucose
Anomeric
carbons
O
CHO
OH
CHO
OH
H+
H2 O
HO
CH2OH
O
HO
OH
OH
CH2OH
OH
OH
CH2OH
D-Glucose
D-Fructose
Sucrose is called a “nonreducing sugar” because there is no free aldehyde group to reduce
(both anomeric carbons form the acetal – thus no equilibrium to free aldehyde or ketone)
Polysaccharides
Polysaccharides are thus merely sugar polymers that have multiple carbohydrates connected
Plants store carbohydrates as polysaccharides in two common forms:
Cellulose is a polysaccharide that has glucose molecules connected with a 1,4-β linkage
OH
O
O
HO
H OH
OH
O
O
OH HO
OH
O
O
OH HO
OH
O
HO
O
OH
O n
β-linkage causes
cellulose to have a
linear shape that
packs very well
source of fiber
Starch also is a polysaccharide with glucose molecules connected 1,4, but with an α linkage
OH
O
HO
O
OH
O
HO
α-linkage causes starch to
have a curved structure that
does not pack well
OH
O
OH
O
HO
OH
O
OH
O
HO
OH
O
OH
O n
Humans have an enzyme
that can break the α-linkage
in starch, but not the βlinkage in cellulose, thus
starch is a source of dietary
sugar but cellulose is not
Glycosides
As observed earlier, when an alcohol reacts with a carbohydrate a stable acetal is formed
(called a glycoside)
CH3OH
HCl
H OH
HO
HO
HO
H
H
H
OH
OH
H3O+, !
H OH
HO
HO
HO
H
Will obtain both α
H and β anomers
OH
OCH3
H
If sugars are used as the nucleophile, then disaccharides and polysaccharides can thus be formed
In addition to alcohols, however, other nucleophiles can react at the anomeric carbon of
carbohydrates to form glycosides including components of RNA and DNA
NH2
CHO
OH
OH
OH
CH2OH
Ribose
N
NH2
N
N
H
N
HO
O
N
N
OH OH
Adenine
N
N
Adenosine
Glycoproteins
If the nucleophile is a protein, then the sugar molecules can be attached to protein chains
(called glycoproteins – often the carbohydrate attached is called a “glycan”)
Glycoproteins are critical components of many cell membranes and play a critical component
in cell-cell interactions at the membrane surface
The attachment of the carbohydrate to the protein is called a “glycosylation”
An extraordinary example is the total synthesis of erythropoietin (EPO), a glycoprotein that increases oxygen by increasing red blood cell production
Rebecca M. Wilson, Suwei Dong, Ping Wang, Samuel J. Danishefsky, Angew. Chem. Int. Ed., 2013, 52, 7646-7665
Glycoproteins
The type of glycoproteins present is the difference between human blood types
Humans can have four different blood types (called A, B, AB or O), the differences between the blood types is simply due to the type of carbohydrates attached to the protein in the cell wall of red blood cells
OH OH
HO
OH
O
HO
O
O
Protein
O
Type O
Trisaccharide
O OH
OH
NH
NH
OH
HO
OH
OH OH
O
HO
O
O
O
O
O
O
OH OH
OH
O
OH
HO
O
O
HO
NH
Why type O is the “universal donor”, all blood types have same trisaccharide core but
types A, B or AB (which has some A and B)
have different appendages
O
O OH
OH
OH
O
HO
OH
Type A
Tetrasaccharide
(same as O with an N-acetyl-D-galactosamine)
O
O
Protein
O
O
OH
OH
O
O
HO
NH
O
O
HO
OH
Type B
Tetrasaccharide
(same as O with D-galactose)
Protein