Bio-organic Chemistry Dr. Supartono, M.S. Harjono, S.Pd. M.Si.

Sugar Chemistry & Glycobiology Sugars are poly-hydroxy aldehydes or ketones Examples of simple sugars that may have existed in the pre-biotic world:

Most sugars, i.e., glyceraldehyde are chiral: sp 3 hybridized C with 4 different substituents The last structure is the Fischer projection: 1)CHO at the top 2)Carbon chain runs downward 3)Bonds that are vertical point down from chiral centre 4)Bonds that are horizontal point up 5)H is not shown: line to LHS is not a methyl group

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

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)

Reactions of Sugars 1)The aldehyde group: a)Aldehydes can be oxidized “reducing sugars” – those that have a free aldehyde (most aldehydes) give a positive Tollen’s test (silver mirror) b)Aldehydes can be reduced

c)Reaction with a Nucleophile Combination of these ideas  Killiani-Fischer synthesis: used by Fischer to correate D/L- glyceraldehyde with threose/erythrose configurations:

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

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

Why do we get cyclic acetals of sugars? (Glucose in open form is << 1%) a)Rearrangement reaction: we exchange a C=O bond for a stronger C-O σ bond  ΔH is favored b)There is little ring strain in 5- or 6- membered rings c)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

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

Mutatrotation

In solution, with acid present (catalytic), get MUTAROTATION: not via the aldehyde, but oxonium ion At equilibrium, ~ 38:62 α:β despite α having an AXIAL OH…WHY? ANOMERIC EFFECT

O lone pair is antiperiplanar to C-O σ bond  GOOD orbital overlap (not the case with the β- anomer) oxonium ion Anomeric Effect