Glycosides
Glycosides
Glycosides
Glycosides have a substituent other than OH at the anomeric carbon.Usually the atom connected to the anomeric carbon is oxygen.
Example
Linamarin is an O-glycoside derived from D-glucose.
OOH
OHHO
HOHOCH2
OOCC
OHHO
HOHOCH2 CH3
N
CH3
D-Glucose
Glycosides
Glycosides have a substituent other than OH at the anomeric carbon.Usually the atom connected to the anomeric carbon is oxygen.Examples of glycosides in which the atom connected to the anomeric carbon is something other than oxygen include S-glycosides and N-glycosides.
Example
Adenosine is an N-glycoside derived from D-ribose
HOCH2
H
OHOH H
OHOHH
D-Ribose
HOCH2
H
NOH H
OHOHH
N
NH2
N
N
Adenosine
Example
Sinigrin is an S-glycoside derived from D-glucose.
OOH
OHHO
HOHOCH2
D-Glucose
OSCCH2CH
OHHO
HOHOCH2
CH2
NOSO3K
Glycosides
O-Glycosides are mixed acetals.
O-Glycosides are mixed acetals
H
OHO
CH O
CH2OH
hemiacetal
H
OROROH
acetal
Preparation of Glycosides
Glycosides of simple alcohols (such as methanol) are prepared by adding an acid catalyst (usually gaseous HCl) to a solution of a carbohydrate in the appropriate alcohol.
Only the anomeric OH group is replaced.
An equilibrium is established between the α and β-glycosides (thermodynamic control). The more stable stereoisomer predominates.
Preparation of Glycosides
HO
CH O
CH2OH
H OHH OH
HH OH
CH3OH
HCl
D-Glucose
OOCH3
OHHO
HOHOCH2
+
O
OCH3
OHHO
HOHOCH2
Preparation of Glycosides
OOCH3
OHHO
HOHOCH2
+
O
OCH3
OHHO
HOHOCH2
Methylβ-D-glucopyranoside
Methylα-D-glucopyranoside
(major product)
Mechanism of Glycoside Formation
HCl
carbocation is stabilized by lone-pair donation from oxygen of the ring
OOH
OHHO
HOHOCH2
••••
O
OHHO
HOHOCH2
+H
•• ••
Mechanism of Glycoside Formation
O
OHHO
HOHOCH2
+H
•• •• O••
H
CH3
••
OO
OHHO
HOHOCH2 •• ••
CH3
H
••++
O
OHHO
HOHOCH2
OHH3C ••
+
Mechanism of Glycoside Formation
OO
OHHO
HOHOCH2 •• ••
CH3
H
••+
+
O
OHHO
HOHOCH2
OHH3C ••
+
+
••
O
OCH3
OHHO
HOHOCH2 •• ••
••
–H+
••O
OCH3
OHHO
HOHOCH2
••
••
••
Disaccharides
Disaccharides
Disaccharides are glycosides.
The glycosidic linkage connects two monosaccharides.
Two structurally related disaccharides are cellobiose and maltose. Both are derived from glucose.
Maltose and Cellobiose
Maltose
Maltose is composed of two glucose units linked together by a glycosidic bond between C-1 of one glucose and C-4 of the other.The stereochemistry at the anomeric carbon of the glycosidic linkage is α.The glycosidic linkage is described as α(1,4)
O
HOCH2 HOCH2
OH
OHHOOHHO
HOO O1 4α
Maltose and Cellobiose
Cellobiose
Cellobiose is a stereoisomer of maltose.The only difference between the two is that cellobiose has a β(1,4) glycosidic bond while that of maltose is α(1,4).
O
HOCH2 HOCH2
OH
OHHOOHHO
HOO O1 4β
Maltose and Cellobiose
CellobioseMaltose
Cellobiose and Lactose
Cellobiose
Cellobiose and lactose are stereoisomeric disaccharides.Both have β(1,4) glycosidic bonds.The glycosidic bond unites two glucose units in cellobiose. It unites galactose and glucose in lactose.
O
HOCH2 HOCH2
OH
OHHOOHHO
HOO O1 4β
Cellobiose and Lactose
Lactose
Cellobiose and lactose are stereoisomeric disaccharides.Both have β(1,4) glycosidic bonds.The glycosidic bond unites two glucose units in cellobiose. It unites galactose and glucose in lactose.
O
HOCH2 HOCH2
OH
OHHOOHHO
HOO O1 4β
Polysaccharides
Cellulose
Cellulose is a polysaccharide composed of several thousand D-glucose units joined by β(1,4)-glycosidic linkages. Thus, it can also be viewed as a repeating collection of cellobiose units.
Cellulose
Four glucose units of a cellulose chain.
Starch
Starch is a mixture of amylose and amylopectin. Amylose is a polysaccharide composed of 100 to several thousand D-glucose units joined by α(1,4)-glycosidic linkages.Amylose is helical both with respect to the pitch of adjacent glucose units and with respect to the overall chain.
Reduction of Carbohydrates
Reduction of Carbohydrates
Carbonyl group of open-chain form is reduced to an alcohol.Product is called an alditol.Alditol lacks a carbonyl group so cannot cyclize to a hemiacetal.
Reduction of D-Galactose
α-D-galactofuranose
β-D-galactofuranose
α-D-galactopyranose
β-D-galactopyranose
CH2OH
H OH
HHO
HHO
H OH
CH O
CH2OH
H OH
HHO
HHO
H OH
CH2OH
D-Galactitol (90%)
reducing agent: NaBH4, H2O(catalytic hydrogenation can also be used)
Oxidation of Carbohydrates
Benedict's Reagent
Benedict's reagent is a solution of the citrate complex of CuSO4 in water. It is used as a test for "reducing sugars." Cu2+ is a weak oxidizing agent.A reducing sugar is one which has an aldehyde function, or is in equilibrium with one that does.A positive test is the formation of a red precipitate of Cu2O.
+ 2Cu2+RCH
O
5HO–+ + Cu2ORCO–
O
3H2O+
Examples of Reducing Sugars
Aldoses: because they have an aldehyde function in their open-chain form.Ketoses: because enolization establishes an equilibrium with an aldose.
CH2OH
C O
R
CHOH
C OH
R
CH
CHOH
R
O
oxidized by Cu2+
Examples of Reducing Sugars
Disaccharides that have a free hemiacetal function.
O
HOCH2 HOCH2
OH
OHHOOHHO
HOO O
Maltose
Examples of Reducing Sugars
Disaccharides that have a free hemiacetal function.
oxidized by Cu2+
O
HOCH2 HOCH2
OHHOOHHO
HOO OH
CH OMaltose
Glycosides are not reducing sugars
O
OCH3
OH
HOHO
HOCH2
Methyl α-D-glucopyranoside lacks a freehemiacetal function; cannot be in equilibriumwith a species having an aldehyde function
Oxidation of Reducing Sugars
The compounds formed on oxidation of reducing sugars are called aldonic acids.Aldonic acids exist as lactones when 5- or 6-membered rings can form.A standard method for preparing aldonic acids uses Br2 as the oxidizing agent.
Oxidation of D-Xylose
HO
H OH
H OH
H
CH O
CH2OH
Br2
H2O
D-Xylose
HO
H OH
H OH
H
CH2OH
CO2H
D-Xylonic acid (90%)
Oxidation of D-Xylose
HO
H OH
H OH
H
CH2OH
CO2H
D-Xylonic acid (90%)
OO
OH
OHHOCH2
O
O
OH
HOHO
+
Nitric Acid Oxidation
Nitric acid oxidizes both the aldehyde function and the terminal CH2OH of an aldose to CO2H.The products of such oxidations are called aldaric acids.
Nitric Acid Oxidation
CH O
CH2OH
H OH
H OH
H
H OH
HO HNO3
60°C
CO2H
H OH
H OH
H
H OH
HO
CO2H
D-Glucaric acid (41%)D-Glucose
Uronic Acids
CH O
CO2H
H OH
H OH
H
H OH
HO
D-Glucuronic acid
HOHO
OH
OH
HO2CO
Uronic acids contain both an aldehyde and a terminal CO2H function.
Cyanohydrin Formation and Carbohydrate Chain Extension
Extending the Carbohydrate Chain
Carbohydrate chains can be extended by using cyanohydrin formation as the key step in C—C bond-making.The classical version of this method is called the Kiliani-Fischer synthesis. The following example is a more modern modification.
α-L-arabinofuranose
β-L-arabinofuranose
α-L-arabinopyranose
β-L-arabinopyranose
CH2OH
HHO
HHO
H OH
CH O
Extending the Carbohydrate Chain
HCN
CH2OH
HO H
HHO
OHH
CN
CHOH
the cyanohydrin is a mixture of two stereoisomers that differ in configuration at C-2; these two diastereomers are separated in the next step
Extending the Carbohydrate Chain
CH2OH
HO H
HHO
OHH
CN
CHOH
CH2OH
HO H
HHO
OHH
H OH
CN
CH2OH
HO H
HHO
OHH
HO H
CN
+separate
L-Mannononitrile L-Gluconononitrile
Extending the Carbohydrate Chain
CH2OH
HO H
HHO
OHH
H OH
CN
L-Mannononitrile
H2, H2O
Pd, BaSO4
L-Mannose(56% from L-arabinose)
CH2OH
HO H
HHO
OHH
H OH
CH O
Likewise...
CH2OH
HO H
HHO
OHH
HO H
CN
L-Gluconononitrile
H2, H2O
Pd, BaSO4
L-Glucose(26% from L-arabinose)
CH2OH
HO H
HHO
OHH
HO H
CH O
Epimerization, Isomerization, and Retro-Aldol Reactions of
Carbohydrates
Enol Forms of Carbohydrates
Enolization of an aldose scrambles the stereochemistry at C-2.This process is called epimerization. Diastereomers that differ in stereochemistry at only one of their stereogenic centers are called epimers.D-Glucose and D-mannose, for example, are epimers.
Epimerization
CH O
CH2OH
H OH
H OH
H
H OH
HO
D-MannoseD-Glucose
CH O
CH2OH
H OH
H OH
H
HO H
HO
Enediol
CH2OH
H OH
H OH
H
OH
HO
CHOH
C
This equilibration can be catalyzed by hydroxide ion.
Enol Forms of Carbohydrates
The enediol intermediate on the preceding slide can undergo a second reaction. It can lead to the conversion of D-glucose or D-mannose (aldoses) to D-fructose (ketose).
Isomerization
Enediol
CH2OH
H OH
H OH
H
OH
HO
CHOH
C
D-Glucose orD-Mannose
CH O
CH2OH
H OH
H OH
HHO
CHOH
D-Fructose
CH2OH
CH2OH
H OH
H OH
HHO
C O
Retro-Aldol Cleavage
When D-glucose 6-phosphate undergoes the reaction shown on the preceding slide, the D-fructose that results is formed as its 1,6-diphosphate.D-Fructose 1,6-diphosphate is cleaved to two 3-carbon products by a reverse aldol reaction.This retro-aldol cleavage is catalyzed by the enzyme aldolase.
Isomerization
D-Fructose1,6-phosphate
CH2OP(O)(OH)2
H OH
H OH
HHO
C O
CH2OP(O)(OH)2
aldolase
H OH
CH2OP(O)(OH)2
CH O
CH2OP(O)(OH)2
C O
CH2OH
Acylation and Alkylation of Hydroxyl Groups in
Carbohydrates
Reactivity of Hydroxyl Groups in Carbohydrates
acylationalkylation
Hydroxyl groups in carbohydrates undergo reactions typical of alcohols.
Example: Acylation of α-D-glucopyranose
O
OHOH
HOHO
HOCH2
+ CH3COCCH3
O O
5
pyridine
O
O
CH3COCH2
O
CH3CO
O
CH3CO
O CH3CO
OOCCH3
(88%)
Example: Alkylation of methyl α-D-glucopyranoside
O
OCH3
OH
HOHO
HOCH2
+ 4CH3I
Ag2O, CH3OH
O
OCH3
CH3O
CH3OCH3O
CH3OCH2
(97%)
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.
O
OCH3
OH
HOHO
HOCH2
OCH3
O
CH3O
CH3OCH3O
CH3OCH2
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.
O
OCH3
CH3O
CH3OCH3O
CH3OCH2
H2O
H+
(mixture of α + β)
O
OHCH3O
CH3OCH3O
CH3OCH2
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.
(mixture of α + β)
O
OHCH3O
CH3OCH3O
CH3OCH2
CH2OCH3
H OH
OCH3H
HCH3O
H OCH3
CH O
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.
CH2OCH3
H OH
OCH3H
HCH3O
H OCH3
CH O
This carbon has OHinstead of OCH3.Therefore,its O was theoxygen in the ring.
Periodic Acid Oxidation of Carbohydrates
Recall Periodic Acid Oxidation
Cleavage of a vicinal diol consumes 1 mol of HIO4.
CC
HO OH
HIO4C O O C+
Vicinal diols are cleaved by HIO4.
Also Cleaved by HIO4
Cleavage of an α-hydroxy carbonyl compound consumes 1 mol of HIO4. One of the products is a carboxylic acid.
CRC
OH
HIO4C O O C+
α-Hydroxy carbonyl compounds
O R
HO
Also Cleaved by HIO4
2 mol of HIO4 are consumed. 1 mole of formic acid is produced.
HIO4R2C O
R'2C O
+
Compounds that contain three contiguouscarbons bearing OH groups
HCOH
O
OH
R2C CH CR'2
OHHO
+
OHOCH2
HO
OH
OCH3
Structure Determination Using HIO4
Distinguish between furanose and pyranose formsof methyl arabinoside
HO
HO
OOH
OCH3
2 vicinal OH groups;consumes 1 mol of HIO4
3 vicinal OH groups;consumes 2 mol of HIO4