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Sugar Chemistry & Glycobiology

Sugar Chemistry & Glycobiology. In Solomons, ch.22 (pp 1073-1084, 1095-1100) Sugars are poly-hydroxy aldehydes or ketones Examples of simple sugars that may have existed in the pre-biotic world:. Most sugars, e.g. glyceraldehyde, are chiral : sp 3 hybridized C with 4 different substituents

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Sugar Chemistry & Glycobiology

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  1. Sugar Chemistry & Glycobiology • In Solomons, ch.22 (pp 1073-1084, 1095-1100) • Sugars are poly-hydroxy aldehydes or ketones • Examples of simple sugars that may have existed in the pre-biotic world:

  2. Most sugars, e.g. glyceraldehyde, are chiral: sp3 hybridized C with 4 different substituents The last structure is the Fischer projection: • CHO at the top • Carbon chain runs downward • Bonds that are vertical point down from chiral centre • Bonds that are horizontal point up • H is not shown: line to LHS is not a methyl group

  3. In (R) glyceraldehyde, H is to the left, OH to the right  D configuration; if OH is on the left, then it is L • D/L does NOT correlate with R/S • Most naturally occurring sugars are D, e.g. D-glucose • (R)-glyceraldehyde is optically active: rotates plane polarized light (def. of chirality) • (R)-D-glyceraldehyde rotates clockwise,  it is the (+) enantiomer, and also d-, dextro-rotatory (rotates to the right-dexter)  (R)-D-(+)-d-glyceraldehyde & its enantiomer is: (S)-L-(-)-l-glyderaldehyde (+)/d & (-)/l do NOT correlate with D/L or R/S

  4. Glyceraldehyde is an aldo-triose (3 carbons) • Tetroses → 4 C’s – have 2 chiral centres • 4 stereoisomers: D/L erythrose – pair of enantiomers D/L threose - pair of enantiomers • Erythrose & threose are diastereomers: stereoisomers that are NOT enantiomers • D-threose & D-erythrose: • D refers to the chiral centre furthest down the chain (penultimate carbon) • Both are (-) even though glyceraldehyde is (+) → they differ in stereochemistry at top chiral centre • Pentoses – D-ribose in DNA • Hexoses – D-glucose (most common sugar)

  5. Reactions of Sugars • The aldehyde group: • Aldehydes can be oxidized “reducing sugars” – those that have a free aldehyde (most aldehydes) give a positive Tollen’s test (silver mirror) • Aldehydes can be reduced An alditol

  6. Biological Redox of Sugars:

  7. Reaction with a Nucleophile • Combination of these ideas  Killiani-Fischer synthesis: used by Fischer to correlate D/L-glyceraldehyde with threose/erythrose configurations:

  8. Reactions (of aldehydes) with Internal Nucleophiles • Glucose forms 6-membered ring b/c all substituents are equatorial, thus avoiding 1,3-diaxial interactions

  9. Can also get furanoses, e.g., ribose: • Ribose prefers 5-membered ring (as opposed to 6) otherwise there would be an axial OH in the 6-membered ring

  10. Why do we get cyclic acetals of sugars? (Glucose in open form is << 1%) • Rearrangement reaction: we exchange a C=O bond for a stronger C-O σ bond  ΔH is favored • There is little ring strain in 5- or 6- membered rings • ΔS: there is some loss of rotational entropy in making a ring, but less than in an intermolecular reaction:1 in, 1 out. ** significant –ve ΔS! ΔG = ΔH - TΔS Favored for hemiacetal Not too bad for cyclic acetal

  11. Anomers • Generate a new chiral centre during hemiacetal formation (see overhead) • These are called ANOMERS • β-OH up (technically, cis to the CH2OH group) • α-OH down (technically, trans to the CH2OH group) • Stereoisomers at C1 diastereomers • α- and β- anomers of glucose can be crystallized in both pure forms • In solution, MUTAROTATION occurs

  12. Mutarotation

  13. In solution, with acid present (catalytic), get MUTAROTATION: not via the aldehyde, but oxonium ion We know which mechanism operates because the isotope oxygen-18 is incorporated from H218O • At equilibrium, ~ 38:62 α:β despite α having an AXIAL OH…WHY? ANOMERIC EFFECT

  14. Anomeric Effect oxonium ion O lone pair is antiperiplanar to C-O σ bond  GOOD orbital overlap and hence stabilized by resonance form (not the case with the β-anomer)

  15. Projections

  16. More Reactions of Sugars • Reactions of OH group(s): • Esterification: • Ethers:

  17. b) Ethers (con’t) • Acetals

  18. c) Acetals (con’t)

  19. These reactions are used for selective protection of one alcohol & activation of another (protecting group chemistry) 1° alcohol is most reactive protect first AZT

  20. e.g, synthesis of sucrose (Lemieux, Alberta) • Can only couple one way—if we don’t protect, get all different coupling patterns • YET nature does this all of the time: enzymes hold molecules together in the correct orientation • Mechanism still goes through an oxonium ion (more on this later)

  21. Selectivity of Anomer Formation in Glycosides • Oxonium ion can often be attacked from both Re & Si faces to give a mixture of anomers. • How do we control this?

  22. This reaction provides a clue to how an enzyme might stabilize an oxonium ion (see later)

  23. Examples of Naturally Occurring di- & oligo- Saccharides Maltose: 2 units of glucose a β sugar α glycoside 1,4-linkage Lactose (milk): galactose + glucose a β sugar β glycoside 1,4-linkage

  24. Sucrose (sugar): glucose + fructofuranose a β sugar α glycoside 1,2-glycosidic bond α-1,6-glycosidic bond Amylopectin (blood cells): an oligosaccharide α-1,4-glycosidic bond

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