Pyranose Ring Conformation: 1 Pyranose Ring Conformation: 4 #06

#06. 2012-01-20

Quiz 1: Thursday 26 Jan 2012 from 11 AM to 12 noon GG Building Ground Floor #06. 2012-01-20 Last class... Clarification on torsion potential: periodicity 2 and 3 Conformer selection, active/inactive conformations, activation by ligands, etc. - alternative models Inter- and intra-molecular interactions Non-covalent / non-bonded interactions Bonded and non-bonded atoms Hard-sphere approximation Steric effect Preference of trans over gauche conformation for bulky groups #06. 2012-01-20 Monosubstituted cyclohexanes

Bulky group is axially Bulky group is equatorially oriented: gauche to both oriented: trans to both vicinal carbon atoms vicinal carbon atoms #06. 2012-01-20 Monosubstituted cyclohexanes

Bulky group is axially Bulky group is equatorially oriented: gauche to both oriented: trans to both vicinal carbon atoms vicinal carbon atoms #06. 2012-01-20 Cis 1,2-disubstituted cyclohexane

Me 4 5 6 Me 3 2 1 #06. 2012-01-20 Trans 1,4-disubstituted cyclohexane

5 6 Me Me 3 2 1 #06. 2012-01-20 What governs the conformational preferences?

Conformation “a” Conformation “b” Unfolded Folded (protein, DNA, RNA)

Monomers (homo/hetero) Oligomer(s) (protein, lipid)

A + B A·B (binding)

∆∆∆G = ∆∆∆H – T ∆∆∆S

Steric criterion – (approximation of) van der Waals interactions Often, van der Waals contribution is not predominant #06. 2012-01-20 Conformation of 1,3,5-trineopentylbenzene

CH 2-tBu

tBu-H2C

CH 2-tBu

Two neopentyl groups are on one side, All the three neopentyl groups are on third on the other side of the ring the same side of the ring

view along the plane of the ring

Nishio & Hirota (1989) Tetrahedron 45:7201 #06. 2012-01-20 Conformation of Ph-CH(Me)-CH 2-tBu

Ph-CH(Me)-X-tBu gauche X= CH 2, CHOH, S, SO, SO 2

Preferred: Tertiary butyl (tBu) group is trans to the methyl group, trans gauche to the phenyl group

Expected solely based on steric criterion: Tertiary butyl (tBu) group is gauche to the methyl group, trans to the phenyl group

Nishio & Hirota (1989) Tetrahedron 45:7201 #06. 2012-01-20 Gauche preference

n-pentane

CH 3-CH 2-CH 2-CH 2-CH 3 CH 3-CH 2-CH 2-CH 2-CH 3

trans to each other trans to each other

Dimethoxymethane

CH 3-O-CH 2-O-CH 3

gauche preferred over trans #06. 2012-01-20 Conformation of n-alkanes: chain length & solvent effect

C6D6 1-Chloronaphthalene

n-Hexane Extended Extended n-Dodecane Open “U” shaped

J Chem Soc Perkin Trans. 2, (2001) 2370-3 (no volume #) Summary #06. 2012-01-20

Steric criterion helps us to rationalize preferred conformations only when van der Waals contribution is predominant Exceptions discussed: 1,3,5-trineopentylbenzene Ph-CHMe-CH2-tBu Dimethoxymethane – anomeric effect n-Decane in different solvents Relationship among monosaccharides – chemists’#06. view 2012-01-20

Notation HCO

H OH = HOCH 2 Glyceraldehyde

HCO HCO

D-series HOCH HOCH 2 2 ET Erythrose Threose

HCO HCO HCO HCO

HOCH 2 HOCH 2 HOCH 2 HOCH 2 Right AXLe Ribose Arabinose Xylose Lyxose

HCO HCO HCO HCO HCO HCO HCO HCO ALL ALTRuists GLadly MAke GUm In GALlon HOCH 2 HOCH 2 HOCH 2 HOCH 2 HOCH 2 HOCH 2 HOCH 2 HOCH 2 TAnks Allose Altrose Glucose Mannose Gulose Idose Galactose Talose #06. 2012-01-20 Different ring forms of glucose

4C 3 ααα-D-Glucopyranose ( 1) ααα-D-Glucofuranose ( E)

D-Glucose

4C 3 βββ-D-Glucopyranose ( 1) βββ-D-Glucofuranose ( E) #06. 2012-01-20 Monosaccharides: glucose, prototypical example

6 1

5 5 4 1 3 2 4 3 2

4C 1C Pyranose ring conformation: 1 Pyranose ring conformation: 4 #06. 2012-01-20 1C Pyranose ring in 4 conformation (cyclodextrin)

C6 C1

C4 C3 C2

Cambridge structural database code: HEZWAK01 Rendered using RasMol 2.7.2 Caira et al., (1994) J Chem Soc Perkin Trans 2:2071 #06. 2012-01-20 Effect of substituents on ring conformation

Xylopyranose derivatives

CSD refcode OACXPF

C4 C5 CSD refcode C3 OBZXYP10 C1 C2 Luger et al., (1979) Carbohydr. Res. 68, 207 Kothe et al., (1979) C5 Acta Cryst. B30, 365

C1 C4 C3 C2 O-acetyl derivative

O-benzoyl derivative #06. 2012-01-20 Idose, an “unusual” monosaccharides

CHO CHO

H OH HOH

HO H H OH

H OH HOH

H OH H OH

CH 2OH CH 2OH

D-Glucose D-Idose (stereoisomer)

βββ-D-Glucose #06. 2012-01-20 Biological systems: L-enantiomer / uronic acid

CHO CHO CHO

HOH H OH H OH

H OH HO H HO H

HO H H OH H OH

H OH HOH HOH

CH 2OH CH 2OH COOH

D-Idose L-Idose L-Iduronic acid

Constituent of glycosaminoglycans (e.g., heparin, heparan sulphate) #06. 2012-01-20 Conformational preferences of idose

4C 1C 2S 1-ααα-L-idopyranose 4-ααα-L-idopyranose O-ααα-L-iduronopyranose

-CH 2OH - axial All 4 –OH - axial Staggered, but not maximally

Considerable fraction of monosaccharide exists in furanose form

Biochemistry by Stryer, L., p257 (2nd ed.) – heparin as anticoagulant #06. 2012-01-20 Skew-boat conformation

skew-boat conformation: atoms i and i+2 out of plane

ααα-L-Iduronic acid (monosaccharide; aldohexose derivative) Skew-boat conformation 2S ( O)

Chair / boat conformations: atoms i and i+3 out of plane #06. 2012-01-20 Pyranose ring in skew-boat conformation

C3 C1

C6 Heparin heptasaccharide C5 C2

Protein database id: 1SR5:NT1 Rendered using RasMol 2.7.2 In complex with antithrombin Nat Struct Mol Biol 2004 11:863 #06. 2012-01-20 Conformation of heparin heptasaccharide

Protein database id: 1SR5:NT1 Rendered using RasMol 2.7.2 In complex with antithrombin Nat Struct Mol Biol 2004 11:863

1. Changes in the conformation of the pyranose rings 2. Rotations around the single bonds, especially those that link the pyranose rings These will alter the spatial positions of the sulfate groups with respect to each other #06. 2012-01-20 Chair-boat transitions in polysaccharides

Polysaccharide elasticity is governed by chair-boat transitions of the glucopyranose ring

Comparison of ααα- and βββ-linked polysaccharides

4C 4C ααα-D-Glucopyranose ( 1) βββ-D-Glucopyranose ( 1)

Nature (1998) 396:661 #06. 2012-01-20 Half-chair conformation

atoms i and i+1 out of plane

ααα-D-Glucose (Glc694) part of a nonasaccharide in complex with D229N-E257Q-cyclodextringlycosyltransferase (CGTase) from Bacillus circulans strain 251 (PDB id 1CXK) 2H Distorted towards a 3-half chair conformation Uitdehaag et al., (1999) Nat Struct Biol 6:432-6 #06. 2012-01-20 Ribose: in solution and in nucleic acids

CHO

H OH βββ-D-Ribofuranose (3E) H OH

H OH

CH 2-OH

D-Ribose

4C βββ-D-Ribopyranose ( 1) #06. 2012-01-20 Distorted conformations of pyranose rings

Nature (2001) 412:835-838

Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate

D J Vocadlo, G J Davies, R Laine, S G Withers

Carbohydrate Research (2001) 331:461-467

Boat conformations: synthesis, NMR spectroscopy and molecular dynamics of methyl 4,6-O-benzylidene-3- deoxy-3-phthalimido-ααα-D-altropyranoside derivatives

B Coxon, R C Reynolds

Examples chosen arbitrarily