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Home , Furanose, Pyranose

Chem 215-216 HH W11-Notes – Dr. Masato Koreeda - Page 1 of 9. Date: March 24, 2011

Chapters 14.8; 23-1, 2, 5, and 7: - Part I

Carbohydrate nomenclature: http://www.chem.qmul.ac.uk/iupac/2carb/

Carbohydrates: e.g., • Polyhydroxylated aldehydes and ketones and their equivalents H O • Important constituents of both plants and animals (CHOH)n • D-: The primary source of energy in the human body CH OH 2 • : possessing six carbon atoms. • : Sugars possessing five carbon atoms. • : Sugars containing an aldehyde group. • : Sugars containing a ketone group. • : Carbohydrates that do not undergo cleavage on hydrolysis (treatment with water) to smaller molecules.

I. Stereochemistry

OH OH H H H OH 6 H 6 H 6 H 4 anomeric carbon 4 4 anomeric carbon HO O HO OH HO O 5 2 5 2 5 2 HO OH HO O HO H 3 1 3 1 H H 3 H 1 axial HO HO H H equatorial H H H HO OH one hemiacetal form of D-glucose open-chain form of D-glucose another hemiacetal form of D-glucose

These are and (C-1) epimers.

Glucose reacts like an aldehyde since small amounts of the open-chain form are present at equilibrium.

Glucose has 4 stereocenters → 24 = 16 stereoisomers possible → 8 pairs of enantiomers

(1) Fischer projection formulas (a) (+)-: configurational reference compound for all monosaccharides

This stereochemistry is defined as "D" if the OH is projected to the right. O H O H O H vertical bonds go in R H OH H C OH C and horizontal bonds H HO CH2OH come out CH2OH CH2OH

D-(+)-glyceraldehyde R-(+)-glyceraldehyde sign of optical rotation at the sodium D-line (589 nm) small upper-case D configurational designation

• S-(-)-Glyceraldehyde has an L-configuration. • D-Stereochemistry and the sign of optical rotation have no direct correlation, although many D sugars are dextrorotatory (d or +). Chem 215-216 HH W11-Notes – Dr. Masato Koreeda - Page 2 of 9. Date: March 24, 2011

I. Stereochemistry (1) Fischer projection (cont’d) The configurational relatioship was established between D-glyceraldehyde and the naturally occurring positive-rotating grape , (+)-glucose.

OH OH OH O OH O 5 5 H 5 OH 4 2 HO 6 4 2 HO 6 4 2 HO 3 1 H 3 1 3 1 D HO HO O D HO HO D HO

D-glucose D- (found in many fruits) D-2- (found in DNA) [an aldohexose] [a ketohexose] [a deoxyaldopentose] (in its open-chain (in its open-chain (in its open-chain aldehyde form) aldehyde form) keto form) ------

The Fischer projection of (+)-glucose • The more oxidized end of the chain (i.e., the aldehyde in this case) on top of the Fischer chain. • The first chiral center from the bottom of the chain determines the configuration (i.e., D or L). "view" through the "view" O O H surface of the paper 1 1 OH H H OH H OH H H OH 2 2 5 3 H HO 6 4 2 H H D-configuration HO 1 3 HO 3 H H OH HO H OH O H OH O H 6 H 4 4 "view" "view" HOH2C OH H OH (+)-glucose 5 5 H OH

zig-zag conformation: 6 CH2OH CH2OH most favorable, all eclipsed! D-(+)-glucose natural conformation not a natural, D-(+)-glyceraldehyde in solution. stable conformation!

For the conversion from the curved, eclipsed chain structure to the Fischer projection:

90° rotation O 1 HO HO OH H OH H OH 6 H H CH OH H H H 2 H 2 6 6 5 4 3 2 HO H H 1 5 H HO 1 5 H HO HO 4 1 H 3 O O HO H OH O H 2 3 OH HO 4 3 H 6 H 4 OH 2 "rotate" along HOH C HO H "rotate" along H the C -C -bond 2 5 OH HO H OH 1 2 the C3-C4-bond Look from this direction through the surface of the paper for the Fischer projection.

Chem 215-216 HH W11-Notes – Dr. Masato Koreeda - Page 3 of 9. Date: March 24, 2011

Carbohydrate families: All aldoses are called “reducing sugars” because of the aldehyde group; they reduce certain metal ions and can be easily oxidized. Two well known reagents for reducing sugars are:

1) Ag(I) → Ag (0) in NaOH/H2O (Tollens test) 2) Cu(II)SO4 (blue) in NaOH/H2O → red Cu2O (Benedict’s reagent)

Note: In addition to aldoses, ketoses are also reducing sugars. α-Hydroxyketones in general react with these reagents and can readily be oxidized.

aldotriose: aldotetraoses: pentoses: O H O H O H O H O H

H OH H OH HO H H OH H OH H OH H OH H OH HO H L! CH OH 2 H OH HO H CH2OH CH2OH CH OH CH OH D-glyceraldehyde D- D- 2 2 D-: found in RNA L-

Hexoses: There are 16 stereoisomers and 8 of these are D-sugars.

Mnemonics for 8 D-aldohexoses:

1 1CHO 2 HO 2 H 3 HO 3 H H 4 HO 4 5 H 5 OH glucose 6 CH2OH All altruists gladly make gum in gallon tanks.

Remember the structures of D-glucose and D-glyceraldehyde. You don’t need to memorize the structures of any other sugars.

1) Which of the eight D-hexoses shown above represent epimeric pairs? 2) Draw the Fischer projection structures of L-glucose, D-galactose (C-4 epimer of D- glucose; a milk sugar), and D-mannose (C-2 epimer of D-glucose). + - 3) Draw the Fischer projection structure of L-alanine, (H3C)-CH(NH3 )C(=O)O .

Chem 215-216 HH W11-Notes – Dr. Masato Koreeda - Page 4 of 9. Date: March 24, 2011

I. Stereochemistry: (1) OH OH H H H OH 6 H β-OH 6 H 6 H 4 H O 4 H O 4 HO 2 HO H 2 HO 5 2 5 2 5 2 HO OH HO O HO H 3 1 3 1 1 axial H H 3 H HO HO H H equatorial H H H HO OH α-OH open-chain form of D-glucose β− α−anomer [α] +18.7° [α] +112° D virtually no concentration of this species D β−D-(+)-glucopyranose in the equilibrium mixture; only a transient α−D-(+)-glucopyranose intermediate. or β−D-glucose or α−D-glucose

• After the equilibrium is reached, the optical rotation of the mixture shows: [α]D +53°.

Therefore, the mixture consists of 63% of β-D- and 37% of α-D-glucopyranose.

Based on: X • 18.7 + (1 - X) • 112 = 53

Note: (1) vs

6-membered ring 5-membered ring O O (HO)n (HO)n OH OH O O pyranose furanose pyran furan

(2) β− vs α−stereochemistry: anomeric stereoisomers (see pages 5-6 for definitions)

Cyclic sugars such as and : the stereochemistry at the anomeric carbon relative to that at the stereo-defining center whether the sugar is D or L. If a D-sugar and the non-ether part of the ring For D-sugars: drawn in front and the ether portion drawn β behind a group (usually OH, OR, or X) O O ponting up at the anomeric center OH H 1 (i.e., at C-1) is defined as β 1 H α and the one pointing down is OH defined as α. non-ether part of the ring For L-sugars: • The C-6 group such as CH2OH, C(=O)OH usually α adopts an equatorial orientation. O O • The or has nothing to do with the axial or OH H α β 1 equatorial orientation of the group attached at C-1. 1 H β • For L-sugars definition is reversed OH axial Examples equatorial equatorial OH HO 6 OH 6 β-OH equatorial 4 H 4 O HO α-OH O 5 OH HO 5 2 HO 2 6 5 O 1 H HO OH HO OH 1 OH 3 1 3 3 H equatorial β-OH OH H 4 2 HO H H HO β−D-glucose enantiomers!! β−L-glucose α−L-glucose

Chem 215-216 HH W11-Notes – Dr. Masato Koreeda - Page 5 of 9. Date: March 24, 2011

α- or β- at the anomeric carbon – Taken from: http://www.chem.qmul.ac.uk/iupac/2carb/06n07.html

The anomeric center: The new center of chirality generated by hemiacetal or hemiketal ring closure is called the anomeric center. The two stereoisomers are referred to as anomers, designated α or β according to the configurational relationship between the anomeric center and a specified anomeric reference atom. The anomeric reference atom and the anomeric configurational symbol (α or β): The anomeric reference atom is the configurational atom of the parent, unless multiple configurational prefixes are used. If multiple configurational prefixes are used, the anomeric reference atom is the highest-numbered atom of the group of chiral centers next to the anomeric center that is involved in the heterocyclic ring and specified by a single configurational prefix. In the α anomer, the exocyclic oxygen atom at the anomeric center is formally cis, in the Fischer projection (i.e., the same side with respect to the carbon main chain), to the oxygen attached to the anomeric reference atom; in the β anomer these oxygen atoms are formally trans. The anomeric symbol α or β, followed by a hyphen, is placed immediately before the configurational symbol D or L of the trivial name or of the configurational prefix.

D-Sugars α! at C-1 1 (anomeric center) configurational H OH CH OH atom (D) 2 H OH H O H 2 H HO 3 H same side of the ring OH H H 4 OH HO OH anomeric reference H O position 5 H OH CH2OH 6 α-D-glucopyranose configurational atom (D)

β! at C-1 configurational (anomeric center) atom (D) CH2OH HO 1 H H O OH H OH 2 H HO H OH H 3 HO and O on the HO H H 4 OH opposite sides of the ring anomeric reference H OH position H 5 O β-D-glucopyranose CH2OH 6 configurational atom (D)

L-Sugar α! at C-1 (anomeric center)

same side of the ring H HO 1 H HO O OH H OH configurational H 2 atom (L) OH H HO H 3 H H anomeric reference HO H position 4 H OH H 5 H configurational atom (L) α-L-arabinopyranose O

Chem 215-216 HH W11-Notes – Dr. Masato Koreeda - Page 6 of 9. Date: March 24, 2011

For simple aldoses up to aldohexoses, and ketoses up to hepto-2-uloses,* the anomeric reference atom and the configurational atom are the same.

β! at C-1 (anomeric center) 1 H3CO H 2 H OH O OCH3 H3CO and OH H OH on the opposite sides 3 4 H HO H configurational of the ring 4 atom (D) H O H H 5 OH 5 H OH anomeric reference H OH position CH2OH CH2OH configurational atom (D) methyl β-D-galactofuranoside

“If multiple configurational prefixes are used, the anomeric reference atom is the highest- numbered atom of the group of chiral centers next to the anomeric center that is involved in the heterocyclic ring and specified by a single configurational prefix. In the α anomer, the exocyclic oxygen atom at the anomeric center is formally cis, in the Fischer projection (i.e., the same side with respect to the carbon main chain), to the oxygen attached to the anomeric reference atom; in the β anomer these oxygen atoms are formally trans. The anomeric symbol α or β, followed by a hyphen, is placed immediately before the configurational symbol D or L of the trivial name or of the configurational prefix.”

α! at C-1 1 same side of the ring (anomeric center) H OCH3 HO H 2 HO 3 H H OH D-manno anomeric reference 4 position H 5 O 7 CH2OH 6 configurational HO 6 H H OH atom (L) L-glycero 5 7 CH2OH H O H H HO 4 OH HO OCH3 H H methyl L-glycero- α-D-manno-heptopyranoside

1 * CH2OH 2 O 3 HO H 4 HO H 5 D-manno- H OH hepto-2-ulose H 6 OH 7 CH2OH Chem 215-216 HH W11-Notes – Dr. Masato Koreeda - Page 7 of 9. Date: March 24, 2011

I. Stereochemistry: (3) Haworth projection formulas above the plane OH of the ring 6 6 H 6 CH2OH CH2OH push down H 4 5 O 5 O HO O H OH 5 2 H H HO H H H 4 OH H 1 4 OH H 1 3 H 1 push up above the plane HO OH H H OH HO 3 2 HO 3 2 of the ring H OH H OH α-D-glucopyranose in the chair form α-D-glucopyranose β-D-glucopyranose in a Haworth projection in a Haworth projection formula formula

(3)-1. Drawing the pyranose (6-membered ring) Haworth projection structure from the Fischer projection structure of D-glucose:

1. Turn the Fischer projection O H 1 on the plane of the paper by 90° clockwise H OH H H OH H 2 O HO H 3 HOH2C H 4 OH HO HO H OH H H 5 OH 2. Curve the Fischer 6 CH2OH HO 6 H H main carbon chain as 1 O The Fischer projection H OH H H CH2 6 O defined. H structure of D-glucose. HOH C H OH 2 5 4 3 2 1 5 H 2 HO HO H OH HO 4 3 OH HO H

3. Rotate along the C4-C5 bond by 120 ° counterclockwise to bring the C5 OH to the same hemiacetal; α-anomer hemiacetal; β-anomer plane as the C1 aldehyde 6 CH OH 6 CH OH 2 2 4. Make the 6-membered make a ring 5 O 5 O OH H H H H H ring by connecting C5-OH 6 1 O H H and C aldehyde C. HOH2C O 4 OH H 1 or 4 OH H 1 1 H 5 H OH 2 HO 3 2 OH HO 3 2 H H 4 3 H OH H OH OH HO α-D-glucopyranose β-D-glucopyranose H Or tie up Curve the chain Alternatively, directly! as defined. Rotate! This may be easier!! 6 H H OH H HOH C H OH H HOH2C H OH H O 2 O O HOH C HO HO 2 5 4 3 2 1 H H H H H H HO HO OH HO OH H HO H OH

Chem 215-216 HH W11-Notes – Dr. Masato Koreeda - Page 8 of 9. Date: March 24, 2011

I. Stereochemistry: (3) Haworth projection formulas (3)-2. Drawing the furanose (5-membered ring) Haworth projection structure from the Fischer projection structure of D-glucose:

O H 1. Turm the Fischer projection 1 on the plane of the paper H OH by 90° clockwise. H H OH H 2 O HOH C HO 3 H 2 HO HO H OH H H 4 OH H 5 OH 6 CH2OH 6 CH OH 2. Curve the Fischer HO 2 H main carbon chain as H H OH H H 5 The Fischer projection 6 O defined (C1 through C5). H HOH C OH H 1 structure of D-glucose. 2 5 4 3 2 1 4 H HO HO H OH HO 3 2 O H OH

3. Rotate along the C3-C4 bond by 120 ° counterclockwise to bring the C4-OH to the same plane as the C-1 aldehyde hemicaetal; α-anomer β-anomer

6 6 HOH C6 make a ring CH2OH CH2OH 2 4. Make the 5-membered H H HO H HO H H HO H OH ring by connecting C4-OH 5 OH H 5 OH H 5 O O O O and C1 aldehyde C. 4 1 or 4 1 HO 1 3 2 3 H 2 4 H OH H H H 2 H HO H HO 3 α-D-glucofuranose β-D-glucofuranose H HO Curve the chain Alternatively, Or connect and 6 as defined. make a ring! HOH C Rotate! HOH2C 2 HO H HO H H H OH H H 5 H O OH O OH HOH C O 2 HO HO H 4 3 2 1 HO O H OH H H OH H H H H H OH (3) Draw the pyranose and furanose structures, both in β-anomeric forms, of L-ketohexose shown below. They exist as hemiketals. answers: 1. Rotate the Fischer projection 1 on the plane of the paper CH2OH by 90° clockwise 6 O 2 O OH OH H 1 H OH 5 2 3 HOH2C CH2OH β-L-pyranose HO H 4 H H OH O 4 3 HO 5 H furanose 6 CH2OH pyranose 1 The Fischer projection O structure of an L- HO OH OH H 5 2 1 4 3 ketohexose. 2 6 6 5 4 3 CH2OH β-L-furanose O H H OH

Chem 215-216 HH W11-Notes – Dr. Masato Koreeda - Page 9 of 9. Date: March 24, 2011

Carbohydrate stereochemistry practice examples

I. Draw the α-pyranose forms and β-furanose forms of each of the following. For pyranose forms draw as a Haworth projection and as a conformational representation (i.e., chair form).

(a) (b) (c) (d) H O H H O O CH2OH C C C O HO H HO H HO H HO H HO H H OH H OH H OH H OH HO H H OH H OH HO H CH2OH CH2OH CH OH 2 CH2OH

II. Draw the open-chain form as a Fischer projection for each of the following.

(a) H (b) HO H (c) OH HO HO O OH CH2OH OH H H H H O H H H C O OH H H H 3 OH H H OH OH H OH H HO H

(e) (d) H O H H H HOH2C O CH2OH OH H H OH OH H OH H OH OH OH CH2OH