Carbohydrate Structure and Nomenclature

“Essentials of Glycobiology”1 April 2004

Nathaniel FinneyDept. of Chemistry and Biochemistry

UCSDnfinney@chem.ucsd.edu

1

Lecture Outline

1. Carbohydrates - definition and need for nomenclature.2. Individual sugars, Fischer projections and shorthand.3. Cyclization of C5/C6 sugars and existence of “anomers.”4. Alternatives to the Fischer projection: Haworth, Mills and chair

representations. Furanose vs. Pyranose sugars, aldo vs. keto sugars,lactones, and more on anomeric configuration.

5. Oligosaccharides: formalisms for describing sugars attached to oneanother.

6. Branched sugars: further complexity and the need for yet another way todescribe oligo- and polysaccharides.

7. Final note on language for stereoisomers, and caveat on conformationalisomerism.

2

Carbohydrates - Definition and Language

Carbohydrates literally named as apparent “hydrates” of carbon.

Glucose, e.g.: C6H12O6 = C(H2O)6.

Seemingly trivial point underscores the need to develop a system for talkingabout and/or representing carbohydrates.

Monosaccharides: single sugars; clear language and numerous pictorial forms.

Oligosaccharides (typically n sugars, n ≤ 10 or so): more complex language,only one of previous pictorial forms remains tractable.

Polysaccharides: systematic language accurate but cumbersome, new pictorialrepresentation most useful.

3

Glyceraldehyde and “Fischer Projections”

Glyceraldehyde, a 3 carbon aldehyde sugar or “aldotriose,” exists as 2 mirrorimage isomers. Initially characterized by optical rotation (ability to rotateplane polarized light). Dextro- and levorotary forms arbitrarily assignedfollowing structures.

This is the origin of D vs. L nomenclature for sugars - does stereocenterfarthest from the aldehyde terminus have the configuration of D- or L-glyceraldehyde?

A “ketotriose:”

CHO

CH2OHOHH

CHO

CH2OHHHO

mirror plane

D-glyceraldehyde D-glyceraldehyde

CH2OH

CH2OHO

4

D-”Alditols” with 4 Carbons

Two possible isomers at each new carbon center.Can complete tautology with a tree diagram.Mentally insert new carbon center between aldehyde terminus (C1) and what

was previously C2.Note that D configuration is retained.

5

D-”Alditols” with 5 Carbons

Note common names for D-sugars - ribose in particular.

6

D-”Alditols” with 6 Carbons

Note common names for D-sugars, along with 3-letter abbreviations.This is a vocabulary exercise.

Gal Man Glc

7

Straight Chain Fischer Structures Miss An Important Feature

Aldehydes, particularly aldehydes with a heteroatom on the adjacent carbon,are very electrophilic. In the case of 5 and 6 carbon sugars, they tend tocyclize:

8

Cyclization Can Produce Multiple Isomers

9

Better 2-D Representations of 3-D Sugars

Moving from Fischer to standard “dash-wedge” formalism - a quick reminder:

CHO

CH2OHOHH

D-glyceraldehyde

CHO

CH2OHOHH

CHO

HOH2C HCHO HOH2C CHO

CHO

10

Better 2-D Representations of 3-D Sugars

From Fischer to Haworth to abbreviated Haworth diagrams.

Imagine walking along the carbon spine of the Fischer projection, notingwhether hydroxyl groups are to the right or left. Now imagine around theperiphery of a flat hexagon. Then get rid of the ugly hydrogen atoms.

11

Better 2-D Representations of 3-D Sugars

Repeating the exercise for a 6 carbon ketose:

Hey - what’s all this business about a and b? We’ll get to that in a minute.First we need to do better than these awful Haworth projections.

12

Better 2-D Representations of 3-D Sugars

Abbreviated Haworth projections are acceptable for individual 5 memberedring sugars. We can (and need) to do better than that for 6 memberedrings.

Here are the Haworth and chair representations for glucose. Note that there are2 chair conformations, although only one is really relevant in this case.

13

A Brief Aside: Mills Structures for Sugars

Mills structures are often preferred by organic chemists for monosaccharides.Its worth making note of them because: 1) you’ll see them again, and 2)they make it easier to see the origin of the terms “furanose” and“pyranose” sugars.

Here are the forms for b-D-glucose, a “pyranose” sugar:

CHOOHHHHOOHHOHH

CH2OH

OHOHO OHOH

OHOOH

OH

HO

HO

CH2OHO

OH

OH

HO OH

OH

Fischer abbreviatedHaworth

chair Mills

O

2H-pyran

14

A Brief Aside: Mills Structures for Sugars

Here are the forms of b-D-ribose, a “furanose” sugar:

CHOOHHOHHOHH

CH2OH

OHHOCH2

HO OH

O OHOCH2 OH

HO OH

O

Fischer abbreviatedHaworth

Mills furan

15

Nomenclature for Pyranose vs. Furanose Forms

An italicized p or f may be appended to the 3 letter name for a sugar to indicatewhether the pyranose or furanose form is being discussed.

16

a vs. b Nomenclature for “Anomers”

We can use the same sugars to note the origin of a vs. b nomenclature inpyranose and furanose sugars. a is used to denote the anomer where theabsolute stereochemistry of the anomeric position and the most remotesterocenter in the sugar chain are the same; b is used for the case wherethey have opposite configurations.

R configuration R configuration S configuration

17

a vs. b Nomenclature for “Anomers”

While you could just memorize a = axial, this is wrong, and particularlymisleading in the case of furanose sugars: in 5 membered rings,conformational preferences are often subtle and the term “axial” can beambiguous.

R configurationR configuration S configuration

18

A Last Bit of Nomenclature for Chair Structures

Although D-glucose has a strong preference for one chair conformation, this isnot true for all sugars. Here’s some (esoteric) nomenclature for describingthe two chair conformations of D-hexoses:

19

What About Oligosaccharides?

How do we describe molecules containing sugars that are attached to oneanother? (We’ll limit our discussion to cases where the anomeric center ofone sugar is attached to an oxygen atom of another sugar - that is, we’lldiscus only “glycosides.”)

There are basically 2 things we need to keep track of: 1) the anomericconfiguration of the “glycosidic linkage,” and 2) the identity of the carbonon the next sugar that shares the bridging oxygen.

Here’s a simple glycoside:

20

What About Oligosaccharides?

Here’s a simple example: maltose, or D-Glc-a(1-4)-D-Glc.

So how did we come up with that name? Once its been agreed which sugar isgoing to be defined first, its pretty self explanatory.

So how do you know which sugar comes first?

O

O O

HO

HO

HO

HOHO

HO

HOOH

maltose

D-Glc-a(1-4)-D-Glc

21

Naming Starts at the “Nonreducing” Terminus

The naming of sugars begins with the sugar farthest from the “reducing”terminus of the oligosaccharide. This terminology derives from very oldsugar chemistry, such as the oxidation of glucose to 1,5-glucono-lactonewith the Tollens Reagent:

In this reaction, the anomeric position is oxidized and Ag(I) is reduced.Glucose is thus called a “reducing sugar,” and the end of theoligosaccharide with a free anomeric position is called the reducingterminus. (The nomenclature is used even if the sugar is protected as aglycoside.)

O

OH

OHOH

HO OH

Ag(I), NaOH O

OH

OOH

HO OH+ Ag(0) (silver mirror)

22

A Quick Aside on Lactone

Here are the Fischer projections and names of some simple sugar-derived acidsand the corresponding cyclic esters (lactones):

23

A Few Final Points

1. Branched sugars are harder to name than straight chain sugars. Namingbegins with the longest continuous chain; sugar siide chains (branches) areincluded parenthetically. If the anomeric position of the reducing end is anacetal, the acetal substituent is denoted last.

24

A Few Final Points

2. There is an alternate pictorial system that it better suited to the synthesis ofvery complex branched structures. In this system, each of the commonsugars is denoted by a geometric shape (circle, square, triangle) whichmay be partially colored in.

25

A Few Final Points

3. Describing the conformation of oligo- and polysaccharides requiresadditional language. Most (but not all) issues of concern relate to theconformational preferences of the glycosidic linkage. The glycosidicconformation of a disaccharide fragment can be uniquely defined by twoangles, f and y:

O

O O

HO

HO

HO

HOHO

HO

HOOH

f is defined by the H1/C-X dihedral angle

y is defined by the HX/C1 dihedral angle

H

26