Carbohydrate Structure and Nomenclature “Essentials of Glycobiology” 1 April 2004 Nathaniel Finney Dept. of Chemistry and Biochemistry UCSD nfinney@chem.ucsd.edu

Lecture Outline Carbohydrates - definition and need for nomenclature. Individual sugars, Fischer projections and shorthand. Cyclization of C5/C6 sugars and existence of “anomers.” Alternatives to the Fischer projection: Haworth, Mills and chair representations. Furanose vs. Pyranose sugars, aldo vs. keto sugars, lactones, and more on anomeric configuration. Oligosaccharides: formalisms for describing sugars attached to one another. Branched sugars: further complexity and the need for yet another way to describe oligo- and polysaccharides. Final note on language for stereoisomers, and caveat on conformational isomerism.

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 talking about 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 pictorial representation most useful.

Glyceraldehyde and “Fischer Projections” Glyceraldehyde, a 3 carbon aldehyde sugar or “aldotriose,” exists as 2 mirror image isomers. Initially characterized by optical rotation (ability to rotate plane polarized light). Dextro- and levorotary forms arbitrarily assigned following structures. This is the origin of D vs. L nomenclature for sugars - does stereocenter farthest from the aldehyde terminus have the configuration of D- or L-glyceraldehyde? A “ketotriose:”

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.

D-”Alditols” with 5 Carbons Note common names for D-sugars - ribose in particular.

D-”Alditols” with 6 Carbons Note common names for D-sugars, along with 3-letter abbreviations. This is a vocabulary exercise. Gal Man Glc

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 to cyclize:

Cyclization Can Produce Multiple Isomers

Better 2-D Representations of 3-D Sugars Moving from Fischer to standard “dash-wedge” formalism - a quick reminder:

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, noting whether hydroxyl groups are to the right or left. Now imagine around the periphery of a flat hexagon. Then get rid of the ugly hydrogen atoms.

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.

Better 2-D Representations of 3-D Sugars Abbreviated Haworth projections are acceptable for individual 5 membered ring sugars. We can (and need) to do better than that for 6 membered rings. Here are the Haworth and chair representations for glucose. Note that there are 2 chair conformations, although only one is really relevant in this case.

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:

A Brief Aside: Mills Structures for Sugars Here are the forms of b-D-ribose, a “furanose” sugar:

Nomenclature for Pyranose vs. Furanose Forms An italicized p or f may be appended to the 3 letter name for a sugar to indicate whether the pyranose or furanose form is being discussed.

a vs. b Nomenclature for “Anomers” We can use the same sugars to note the origin of a vs. b nomenclature in pyranose and furanose sugars. a is used to denote the anomer where the absolute stereochemistry of the anomeric position and the most remote sterocenter in the sugar chain are the same; b is used for the case where they have opposite configurations.

a vs. b Nomenclature for “Anomers” While you could just memorize a = axial, this is wrong, and particularly misleading in the case of furanose sugars: in 5 membered rings, conformational preferences are often subtle and the term “axial” can be ambiguous.

A Last Bit of Nomenclature for Chair Structures Although D-glucose has a strong preference for one chair conformation, this is not true for all sugars. Here’s some (esoteric) nomenclature for describing the two chair conformations of D-hexoses:

What About Oligosaccharides? How do we describe molecules containing sugars that are attached to one another? (We’ll limit our discussion to cases where the anomeric center of one sugar is attached to an oxygen atom of another sugar - that is, we’ll discus only “glycosides.”) There are basically 2 things we need to keep track of: 1) the anomeric configuration of the “glycosidic linkage,” and 2) the identity of the carbon on the next sugar that shares the bridging oxygen. Here’s a simple glycoside:

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 is going to be defined first, its pretty self explanatory. So how do you know which sugar comes first?

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 old sugar chemistry, such as the oxidation of glucose to 1,5-glucono-lactone with 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 the oligosaccharide with a free anomeric position is called the reducing terminus. (The nomenclature is used even if the sugar is protected as a glycoside.)

A Quick Aside on Lactone Here are the Fischer projections and names of some simple sugar-derived acids and the corresponding cyclic esters (lactones):

A Few Final Points 1. Branched sugars are harder to name than straight chain sugars. Naming begins with the longest continuous chain; sugar siide chains (branches) are included parenthetically. If the anomeric position of the reducing end is an acetal, the acetal substituent is denoted last.

A Few Final Points 2. There is an alternate pictorial system that it better suited to the synthesis of very complex branched structures. In this system, each of the common sugars is denoted by a geometric shape (circle, square, triangle) which may be partially colored in.

A Few Final Points 3. Describing the conformation of oligo- and polysaccharides requires additional language. Most (but not all) issues of concern relate to the conformational preferences of the glycosidic linkage. The glycosidic conformation of a disaccharide fragment can be uniquely defined by two angles, f and y: