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Home , Aldose, Furanose, Pyranose, Xylose

25.17 Structure Determination Carbohydrate Structure Determination

Spectroscopy X-Ray Crystallography Chemical Tests once used extensively; now superceded by spectroscopic methods and x-ray crystallography reactions of can involve either open-chain form, , or form 25.18 Reduction of Carbohydrates Reduction of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 so cannot cyclize to a . Reduction of D-

reducing agent: NaBH4, H2O (catalytic can also be used)

CH O CH2OH a-D-galactofuranose H OH H OH b-D-galactofuranose HO H HO H a-D-galactopyranose HO H HO H b-D-galactopyranose H OH H OH

CH2OH CH2OH

D-Galactitol (90%) 25.19 Oxidation of Carbohydrates Benedict's Reagent

O O

+ 2+ – – + RCH + 2Cu + 5HO RCO + Cu2O + 3H2O

Benedict's reagent is a solution of the citrate complex of

CuSO4 in water. It is used as a test for "reducing ." Cu2+ is a weak oxidizing agent. A reducing is one which has an function, or is in equilibrium with one that does. A positive test is the formation of a red precipitate of

Cu2O. Examples of Reducing Sugars

Aldoses: because they have an aldehyde function in their open-chain form. : because enolization establishes an equilibrium with an .

CH2OH CHOH CH O C O C OH CHOH R R R

oxidized by Cu2+ Examples of Reducing Sugars

Disaccharides that have a free hemiacetal function.

HOCH2 HOCH2 O O HO O OH

HO OH HO OH Examples of Reducing Sugars

Disaccharides that have a free hemiacetal function.

HOCH2 HOCH2 O OH Maltose HO O CH O

HO OH HO OH

oxidized by Cu2+ Glycosides are not reducing sugars

HOCH2 HO O HO OH OCH3

Methyl a-D-glucopyranoside lacks a free hemiacetal function; cannot be in equilibrium with 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-

CH O CO2H H OH H OH Br HO H 2 HO H H O H OH 2 H OH

CH2OH CH2OH

D-Xylose D-Xylonic acid (90%) Oxidation of D-Xylose

O HO CO H HO 2 OH O H OH + HO H H OH HOCH 2 O OH O CH2OH

D-Xylonic acid (90%) OH 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 CO2H H OH H OH HNO HO H 3 HO H

H OH 60°C H OH H OH H OH

CH2OH CO2H

D- D-Glucaric acid (41%) Uronic Acids

Uronic acids contain both an aldehyde and a

terminal CO2H function. CH O

OH H HO2C O HO H HO H OH HO OH H OH OH

CO2H D- 25.20 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. Extending the Carbohydrate Chain

CN CH O a-L-arabinofuranose CHOH b-L-arabinofuranose H OH HCN H OH a-L-arabinopyranose HO H HO H b-L-arabinopyranose HO H HO H

CH2OH CH2OH

the resulting cyanohydrin is a mixture of two stereoisomers that differ in configuration at C-2; these two are separated in the next step Extending the Carbohydrate Chain

CN CN CN

H OH HO H CHOH separate H OH H OH H OH H + H HO H HO H HO H HO H HO H HO H

CH2OH CH2OH CH2OH

L-Mannononitrile L-Gluconononitrile Extending the Carbohydrate Chain

CN CH O

H OH H OH

H OH H2, H2O H OH HO H HO H Pd, BaSO4 HO H HO H

CH2OH CH2OH

L-Mannononitrile L- (56% from L-) Likewise...

CN CH O

HO H HO H

H OH H2, H2O H OH HO H HO H Pd, BaSO4 HO H HO H

CH2OH CH2OH

L-Gluconononitrile L-Glucose (26% from L-arabinose) 25.21 Epimerization, Isomerization, and Retro-Aldol Reactions of Carbohydrates 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 CHOH CH O

H OH C OH HO H HO H HO H HO H H OH H OH H OH H OH H OH H OH

CH2OH CH2OH CH2OH

D-Glucose Enediol D-Mannose 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 () to D- (). Isomerization

CH O CHOH CH2OH

CHOH C OH C O HO H HO H HO H H OH H OH H OH H OH H OH H OH

CH2OH CH2OH CH2OH

D-Glucose or Enediol D-Fructose D-Mannose Retro-Aldol Cleavage

The D-fructose 6-phosphate formed according to the preceding slide undergoes phosphorylation of its free CH2OH group to give D-fructose 1,6-diphosphate. D-Fructose 1,6-diphosphate is cleaved to two 3- products by a reverse aldol reaction. This retro-aldol cleavage is catalyzed by the aldolase. Isomerization

CH2OP(O)(OH)2 CH2OP(O)(OH)2 C O C O aldolase HO H CH2OH H OH H OH CH O H OH CH2OP(O)(OH)2

D-Fructose CH2OP(O)(OH)2 1,6-phosphate 25.22 Acylation and Alkylation of Hydroxyl Groups in Carbohydrates Reactivity of Hydroxyl Groups in Carbohydrates

Hydroxyl groups in carbohydrates undergo reactions typical of alcohols. acylation alkylation Example: Acylation of a-D-glucopyranose O O HOCH2 HO O + 5 CH3COCCH3 HO OH OH Example: Acylation of a-D-glucopyranose O O HOCH2 HO O + 5 CH3COCCH3 HO OH OH pyridine O O CH 3COCH2 O CH3CO CH CO 3 (88%) CH CO O 3 OCCH3 O O Example: Alkylation of methyl a-D-glucopyranoside

HOCH2 HO O + 4CH3I HO OH OCH3

Ag2O, CH3OH Example: Alkylation of methyl a-D-glucopyranoside

HOCH2 HO O + 4CH3I HO OH OCH3

Ag2O, CH3OH

CH3OCH2 O CH3O (97%) CH3O

CH3O OCH3 Classical Method for Ring Size

Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.

CH OCH HOCH2 3 2 O O HO O CH3O HO CH3O

OH CH3O OCH OCH3 3 Classical Method for Ring Size

Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.

CH3OCH2 CH3OCH2 O O CH3O H2O CH3O CH3O CH3O H+ CH3O CH3O OH OCH3 (mixture of a + b) Classical Method for Ring Size

Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.

CH O

H OCH3 CH3OCH2 O CH3O H CH3O

CH3O H OCH3

CH3O H OH OH

(mixture of a + b) CH2OCH3 Classical Method for Ring Size

Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.

CH O

H OCH3 This carbon has OH CH3O H instead of OCH . 3 H OCH Therefore,its O was the 3 oxygen in the ring. H OH

CH2OCH3 25.23 Periodic Acid Oxidation of Carbohydrates Recall Periodic Acid Oxidation

Section 15.12: Vicinal diols are cleaved by HIO4.

HIO4 C C C O + O C

HO OH

Cleavage of a vicinal diol consumes 1 mol of

HIO4. Also Cleaved by HIO4

a-Hydroxy carbonyl compounds

O R HIO4 RC C C O + O C

OH HO

Cleavage of an a-hydroxy carbonyl compound consumes 1 mol of HIO4. One of the products is a carboxylic acid. Also Cleaved by HIO4

Compounds that contain three contiguous bearing OH groups O R C CH R2C CH CR'2 HIO4 R2C O + HCOH HO OH OH

+ R'2C O

2 mol of HIO4 are consumed. 1 mole of formic acid is produced. Structure Determination Using HIO4

Distinguish between furanose and pyranose forms of methyl arabinoside

OH HOCH 2 OH O O HO

OCH3 HO HO OCH3

2 vicinal OH groups; 3 vicinal OH groups; consumes 1 mol of HIO4 consumes 2 mol of HIO4