Importance of Carbohydrates • Distributed widely in nature • Key intermediates of metabolism () • Structural components of plants () • 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 • is produced in plants through photosynthesis from CO2 and H2O • Glucose is converted in plants to other small sugars and polymers (cellulose, ) • Dietary carbohydrates provide the major source of energy required by organisms 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 differ only at the top two carbons. Carbohydrates

Simple carbohydrates are .

Complex carbohydrates are , , and

Polyhydroxy aldehydes are . Polyhydroxy ketones are . Classificaon 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 • (table ): from two monosaccharides (glucose linked to fructose), • Cellulose is a of several thousand glucose units connected by acetal linkages (aldehyde and alcohol) The Smallest Enanomers of 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 configuraon (+) and (–) indicate how the compound rotates the plane of polarized light. Aldoses and Ketoses

• aldo- and keto- prefixes idenfy the nature of the carbonyl group • -ose suffix designates a • Number of C’s in the indicated by root (tri-, tet-, pent-, hex-) Naturally Occurring D Sugars The Aldotetroses

The aldotetroses have two asymmetric centers and four stereoisomers. Configuraons of the Aldoses

• Stereoisomeric aldoses are disnguished by trivial names, rather than by systemac designaons

• Enanomers have the same names but different D,L prefixes

• R,S designaons are difficult to work with when there are mulple similar chirality centers

• Systemac methods for drawing and recalling structures are based on the use of Fischer projecons • Aldotetroses have two chirality centers • There are 4 stereoisomeric aldotetroses, two pairs of enanomers: and threose • D-erythrose is a of D-threose and L-threose

• Aldopentoses have three chirality centers and 23 = 8 stereoisomers, four pairs of enanomers: , , , and

Epimers

Epimers differ in configuraon at one asymmetric center.

D- is a C-2 epimer of d-glucose. D- is a C-4 epimer of d-glucose. Base-Catalyzed Epimerizaon Base-Catalyzed Enediol Rearrangement Reducon

An aldose forms one alditol. A forms two alditols. Oxidaon 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 Oxidaon 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) – Oxidaons generate metal mirrors; serve as tests for “reducing” sugars (produce metallic mirrors) • Ketoses are reducing sugars if they can isomerize to aldoses Oxidaon 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 Degradaon

The Wohl degradaon 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.

Oxidaon of (+)-glucose and (+)-mannose forms opcally acve 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 opcally acve.

Therefore, (+)-glucose and (+)-mannose are sugars 3 and 4. Determining the Structure of Glucose Cyclic Structures of Monosaccharides:

• 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 Five-Membered Ring Sugars are Called 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 configuraon from glucose at C-3 and C-4, so has the OH groups at C-3 and C-4 in axial posions. Glycoside Formaon

• 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 Formaon Glycosides • Carbohydrate acetals are named by first cing the alkyl group and then replacing the -ose ending of the sugar with –oside • Stable in water, requiring acid for hydrolysis Selecve Formaon of C1-Acetal • Synthesis requires disnguishing the numerous – OH groups • Treatment of glucose pentaacetate with HBr converts anomeric OH to Br • Addion of alcohol (with Ag2O) gives a β glycoside (Koenigs–Knorr reacon) Koenigs-Knorr Reacon Mechanism

• α and β anomers of tetraacetyl-D-glucopyranosyl bromide give β -glycoside • Suggests either bromide leaves and caon is stabilized by neighboring acetyl nucleophile from α side • Incoming alcohol displaces acetyl oxygen to give β glycoside Formaon of N-Glycosides The Eight Essenal Monosaccharides

• Cells need eight monosaccharides for proper funconing • More energecally efficient to obtain these from environment • Include L-, D-galactose, D-glucose, D-mannose, N- acetyl-D-glucosamine, N-acetyl-D-galactosamine, D- xylose, N-acetyl-D- The Eight Essenal Monosaccharides (Connued) The Anomeric Effect

The anomeric effect is the preference of certain substuents bonded to the anomeric carbon for the axial posion. Disaccharides • A disaccharide combines a hydroxyl of one monosaccharide in an acetal linkage with another • A between C1 of the first sugar (α or β) and the –OH at C4 of the second sugar is parcularly common (a 1,4ʹ link) Reducing and Nonreducing Sugars

+ A 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 is a disaccharide. Maltose is a reducing sugar. Maltose and

• 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 mutarotaon

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 mutarotaon • It is 1,4’-β-D-galactopyranosyl-D-glucopyranoside • The structure is cleaved in digeson 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 mutarotaon (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

• Starch is a 1,4ʹ-α-glupyranosyl-glucopyranoside polymer • It is digested into glucose • There are two components – , insoluble in water – 20% of starch • 1,4’-α-glycoside polymer – amylopecn, soluble in water – 80% of starch Amylopecn • More complex in structure than amylose • Has 1,6ʹ-α-glycoside branches approximately every 25 glucose units in addion to 1,4ʹ-α-links Glycogen • A polysaccharide that serves the same energy storage funcon in animals that starch serves in plants • Highly branched and larger than amylopecn—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 selecve • 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 , and then extended Some Other Important Carbohydrates

• Deoxy sugars have an –OH group is replaced by an –H. – Derivaves of 2- are the fundamental units of DNA (deoxyribonucleic acid) Amino Sugars

• –OH group that is replaced by an –NH2 • Amino sugars are found in anbiocs such as streptomycin and gentamicin Cell-Surface Carbohydrates and Influenza Viruses

• Polysaccharides are centrally involved in cell– cell recognion - how one type of cell disnguishes 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 Angenic Determinants The Synthesis of Vitamin C