Carbohydrates Importance of Carbohydrates • Distributed widely in nature • Key intermediates of metabolism (sugars) • Structural components of plants (cellulose) • Central to materials of industrial products: paper, lumber, fibers • Key component of food sources: sugars, flour, vegetable fiber • Contain OH groups on most carbons in linear chains or in rings Sources • Glucose is produced in plants through photosynthesis from CO2 and H2O • Glucose is converted in plants to other small sugars and polymers (cellulose, starch) • Dietary carbohydrates provide the major source of energy required by organisms Chemical Formula and Name
• Carbohydrates have roughly as many O’s as C’s (highly oxidized) • Since H’s are connected to each H and O the empirical formulas are roughly (C(H2O))n – Appears to be “carbon hydrate” from formula • Current terminology: natural materials that contain many hydroxyls and other oxygen-containing groups Carbohydrates are Polyhydroxy Aldehydes or Polyhydroxy Ketones
molecular formula = Cn(H2O)n The structures of glucose and fructose differ only at the top two carbons. Carbohydrates
Simple carbohydrates are monosaccharides.
Complex carbohydrates are disaccharides, oligosaccharides, and polysaccharides
Polyhydroxy aldehydes are aldoses. Polyhydroxy ketones are ketoses. Classifica on of Carbohydrates
• Simple sugars (monosaccharides) can't be converted into smaller sugars by hydrolysis. • Carbohydrates are made of two or more simple sugars connected as acetals (aldehyde and alcohol), oligosaccharides, and polysaccharides • Sucrose (table sugar): disaccharide from two monosaccharides (glucose linked to fructose), • Cellulose is a polysaccharide of several thousand glucose units connected by acetal linkages (aldehyde and alcohol) The Smallest Aldose Enan omers of Glyceraldehyde D-Sugars and L-Sugars An L-Sugar is the Mirror Image of a D-Sugar D and L are Not Related to (+) and (–)
D and L indicate configura on (+) and (–) indicate how the compound rotates the plane of polarized light. Aldoses and Ketoses
• aldo- and keto- prefixes iden fy the nature of the carbonyl group • -ose suffix designates a carbohydrate • Number of C’s in the monosaccharide indicated by root (tri-, tet-, pent-, hex-) Naturally Occurring D Sugars The Aldotetroses
The aldotetroses have two asymmetric centers and four stereoisomers. Configura ons of the Aldoses
• Stereoisomeric aldoses are dis nguished by trivial names, rather than by systema c designa ons
• Enan omers have the same names but different D,L prefixes
• R,S designa ons are difficult to work with when there are mul ple similar chirality centers
• Systema c methods for drawing and recalling structures are based on the use of Fischer projec ons • Aldotetroses have two chirality centers • There are 4 stereoisomeric aldotetroses, two pairs of enan omers: erythrose and threose • D-erythrose is a diastereomer of D-threose and L-threose
• Aldopentoses have three chirality centers and 23 = 8 stereoisomers, four pairs of enan omers: ribose, arabinose, xylose, and lyxose
Epimers
Epimers differ in configura on at one asymmetric center.
D-mannose is a C-2 epimer of d-glucose. D-galactose is a C-4 epimer of d-glucose. Base-Catalyzed Epimeriza on Base-Catalyzed Enediol Rearrangement Reduc on
An aldose forms one alditol. A ketose forms two alditols. Oxida on to an Aldonic Acid
Only aldehydes can be reduced by Br2. Ketones and alcohols cannot be oxidized by Br2. Aldoses and Ketoses are Oxidized by Tollens Reagent Oxida on of Monosaccharides
• Aldoses are easily oxidized to carboxylic acids by: Tollens' + 2+ reagent (Ag , NH3), Fehling's reagent (Cu , sodium tartrate), Benedict`s reagent (Cu2+ sodium citrate) – Oxida ons generate metal mirrors; serve as tests for “reducing” sugars (produce metallic mirrors) • Ketoses are reducing sugars if they can isomerize to aldoses Oxida on to an Aldaric Acid The Kiliani–Fischer Synthesis
The Kiliani–Fischer synthesis increases the carbon chain of an aldose by one carbon.
The Kiliani–Fischer synthesis forms a pair of C-2 epimers. The Wohl Degrada on
The Wohl degrada on decreases the carbon chain of an aldose by one carbon. Determining the Structure of Glucose
A Kiliani–Fischer synthesis on (–)-arabinose forms (+)-glucose and (+)-mannose.
Therefore, (+)-glucose and (+)-mannose are C-2 epimers.
Oxida on of (+)-glucose and (+)-mannose forms op cally ac ve aldaric acids.
Therefore, (+)-glucose and (+)-mannose are sugars 3 and 4, or 5 and 6. Determining the Structure of Glucose
The aldaric acid of (–)-arabinose is op cally ac ve.
Therefore, (+)-glucose and (+)-mannose are sugars 3 and 4. Determining the Structure of Glucose Cyclic Structures of Monosaccharides: Anomers
• Alcohols add reversibly to aldehydes and ketones, forming hemiacetals Monosaccharides Form Cyclic Hemiacetals
D-glucose exists in three different forms α-D-Glucose and β-D-Glucose are Anomers Monosaccharides Form Cyclic Hemiacetals Six-Membered Ring Sugars are Called Pyranoses Five-Membered Ring Sugars are Called Furanoses Furanoses and Pyranoses α-D-Glucose β-D-Glucose Glucose is the Most Stable Aldohexose Galactose is a C-4 Epimer of Glucose, so the OH at C-4 is Axial An L-Sugar is the Mirror Image of a D-Sugar
Gulose differs in configura on from glucose at C-3 and C-4, so gulose has the OH groups at C-3 and C-4 in axial posi ons. Glycoside Forma on
• Treatment of a monosaccharide hemiacetal with an alcohol and an acid catalyst yields an acetal in which the anomeric –OH has been replaced by an –OR group – β-D-glucopyranose with methanol and acid gives a mixture of α and β methyl D-glucopyranosides Mechanism for Glycoside Forma on Glycosides • Carbohydrate acetals are named by first ci ng the alkyl group and then replacing the -ose ending of the sugar with –oside • Stable in water, requiring acid for hydrolysis Selec ve Forma on of C1-Acetal • Synthesis requires dis nguishing the numerous – OH groups • Treatment of glucose pentaacetate with HBr converts anomeric OH to Br • Addi on of alcohol (with Ag2O) gives a β glycoside (Koenigs–Knorr reac on) Koenigs-Knorr Reac on Mechanism
• α and β anomers of tetraacetyl-D-glucopyranosyl bromide give β -glycoside • Suggests either bromide leaves and ca on is stabilized by neighboring acetyl nucleophile from α side • Incoming alcohol displaces acetyl oxygen to give β glycoside Forma on of N-Glycosides The Eight Essen al Monosaccharides
• Cells need eight monosaccharides for proper func oning • More energe cally efficient to obtain these from environment • Include L-fucose, D-galactose, D-glucose, D-mannose, N- acetyl-D-glucosamine, N-acetyl-D-galactosamine, D- xylose, N-acetyl-D-neuraminic acid The Eight Essen al Monosaccharides (Con nued) The Anomeric Effect
The anomeric effect is the preference of certain subs tuents bonded to the anomeric carbon for the axial posi on. Disaccharides • A disaccharide combines a hydroxyl of one monosaccharide in an acetal linkage with another • A glycosidic bond between C1 of the first sugar (α or β) and the –OH at C4 of the second sugar is par cularly common (a 1,4ʹ link) Reducing and Nonreducing Sugars
+ A reducing sugar can reduce Ag or Br2.
+ A nonreducing sugar cannot reduce Ag or Br2.
A sugar with an aldehyde, a ketone, or a hemiacetal group is a reducing sugar.
A sugar without one of these groups is a nonreducing sugar. Maltose
Maltose is a disaccharide. Maltose is a reducing sugar. Maltose and Cellobiose
• Maltose: two D- glucopyranose units with a 1,4ʹ-α-glycoside bond (from starch hydrolysis) • Cellobiose: two D- glucopyranose units with a 1,4ʹ-β-glycoside bond (from cellulose hydrolysis) Hemiacetals in Disaccharides • Maltose and cellobiose are both reducing sugars • The α and β anomers equilibrate, causing mutarota on Lactose
Lactase is the enzyme that cleaves the glycosidic bond in lactose.
Without lactase, lactose is turned into gases by flora in the lower bowel, producing flatulence and stomach cramps. Lactose
• A disaccharide that occurs naturally in milk • Lactose is a reducing sugar. It exhibits mutarota on • It is 1,4’-β-D-galactopyranosyl-D-glucopyranoside • The structure is cleaved in diges on to glucose and galactose Sucrose
Sucrose is not a reducing sugar. Sucrose • “Table Sugar” is pure sucrose, a disaccharide that hydrolyzes to glucose and fructose • Not a reducing sugar and does not undergo mutarota on (not a hemiacetal) • Connected as acetal from both anomeric carbons (aldehyde to ketone) Polysaccharides and Their Synthesis
• Complex carbohydrates in which very many simple sugars are linked • Cellulose and starch are the two most widely occurring polysaccharides Cellulose
• Consists of thousands of D-glucopyranosyl 1,4ʹ-β- glucopyranosides as in cellobiose • Cellulose molecules form a large aggregate structures held together by hydrogen bonds • Cellulose is the main component of wood and plant fiber Starch and Glycogen
• Starch is a 1,4ʹ-α-glupyranosyl-glucopyranoside polymer • It is digested into glucose • There are two components – amylose, insoluble in water – 20% of starch • 1,4’-α-glycoside polymer – amylopec n, soluble in water – 80% of starch Amylopec n • More complex in structure than amylose • Has 1,6ʹ-α-glycoside branches approximately every 25 glucose units in addi on to 1,4ʹ-α-links Glycogen • A polysaccharide that serves the same energy storage func on in animals that starch serves in plants • Highly branched and larger than amylopec n—up to 100,000 glucose units Synthesis of Polysaccharides – via Glycals
• Difficult to do efficiently, due to many –OH groups • Glycal assembly is one approach to being selec ve • Protect C6 –OH as silyl ether, C3–OH and C4–OH as cyclic carbonate • Glycal C=C is converted to epoxide Glycal Coupling
• React glycal epoxide with a second glycal having a free –OH (with ZnCl2 catayst) yields a disaccharide • The disaccharide is a glycal, so it can be epoxidized and coupled again to yield a trisaccharide, and then extended Some Other Important Carbohydrates
• Deoxy sugars have an –OH group is replaced by an –H. – Deriva ves of 2-deoxyribose are the fundamental units of DNA (deoxyribonucleic acid) Amino Sugars
• –OH group that is replaced by an –NH2 • Amino sugars are found in an bio cs such as streptomycin and gentamicin Cell-Surface Carbohydrates and Influenza Viruses
• Polysaccharides are centrally involved in cell– cell recogni on - how one type of cell dis nguishes itself from another
• Small polysaccharide chains, covalently bound by glycosidic links to hydroxyl groups on proteins (glycoproteins), act as biochemical markers on cell surfaces, determining such things as blood type Structures of the A, B, and O Blood-Group An genic Determinants The Synthesis of Vitamin C