Sugar Chemistry

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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

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• 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

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• 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-glyderald
  ehyde
• ()/d (-)/l do NOT correlate with D/L or R/S

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• Glyceraldehyde is an aldo-triose (3 carbons)
• Tetroses ? 4 Cs 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)

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Reactions of Sugars

• The aldehyde group
• Aldehydes can be oxidized
• reducing sugars those that have a free
  aldehyde (most aldehydes) give a positive
  Tollens test (silver mirror)
• Aldehydes can be reduced

An alditol
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Biological Redox of Sugars
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• Reaction with a Nucleophile
• Combination of these ideas ? Killiani-Fischer
  synthesis used by Fischer to correlate
  D/L-glyceraldehyde with threose/erythrose
  configurations

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Reactions (of aldehydes) with Internal
Nucleophiles

• Glucose forms 6-membered ring b/c all
  substituents are equatorial, thus avoiding
  1,3-diaxial interactions

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• 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

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• Why do we get cyclic acetals of sugars? (Glucose
  in open form is ltlt 1)
• Rearrangement reaction we exchange a CO bond
  for a stronger C-O s bond ? ?H is favored
• There is little ring strain in 5- or 6- membered
  rings
• ?S there is some loss of rotational entropy in
  making a ring, but less than in an intermolecular
  reaction1 in, 1 out.

significant ve ?S! ??G ?H -
T?S
Favored for hemiacetal
Not too bad for cyclic acetal
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Anomers

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

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Mutarotation
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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, 3862 aß despite a having an
  AXIAL OHWHY? ANOMERIC EFFECT

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Anomeric Effect
oxonium ion
O lone pair is antiperiplanar to C-O s bond ?
GOOD orbital overlap and hence stabilized by
resonance form (not the case with the ß-anomer)
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Projections
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More Reactions of Sugars

• Reactions of OH group(s)
• Esterification
• Ethers

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b) Ethers (cont)

1. Acetals

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c) Acetals (cont)
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• These reactions are used for selective protection
  of one alcohol activation of another
  (protecting group chemistry)

1 alcohol is most reactive ?protect first
AZT
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e.g, synthesis of sucrose (Lemieux, Alberta)

• Can only couple one wayif we dont 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)

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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?

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This reaction provides a clue to how an enzyme
might stabilize an oxonium ion (see later)
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Examples of Naturally Occurring di- oligo-
Saccharides
Maltose 2 units of glucose a ß sugar a
glycoside 1,4-linkage
Lactose (milk) galactose glucose a ß sugar
ß glycoside 1,4-linkage
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Sucrose (sugar) glucose fructofuranose a ß
sugar a glycoside 1,2-glycosidic bond
a-1,6-glycosidic bond
Amylopectin (blood cells) an oligosaccharide

a-1,4-glycosidic bond