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Carbohydrates
Reducing sugars
Modified monosaccharides
Glycosides
Disaccharides
Glycogen
Polysaccharides
Glycosaminoglycans
Proteoglycans – lubricants and structural components of
connective tissues, mediate adhesion of cells and bind cell
proliferation factors
Biosynthesis of glycosides - glycosyltransferases
Structure of A, B and O oligosaccharide antigens
Glycoproteins
Components of cell membranes
N-linked oligosaccharides
Elastase, sectered glycoprotein (protease)
Assembly of oligosaccharide procursors fro dolichol donors in
Endoplasmatic retuculum
Lectins - carbohydrate-binding proteins
Facilitate cell- cell contact
Carbohydrade Recognition at Infection Site
Development of carbohydrate-based vaccines
Metabolism of carbohydrates
Glycogen
Glycogen phosphorylase
a-1,6-Glucosidase
Glycogen phosphorylase
Glycolysis
Phosphoglucose isomerase
Mechanism of triose phosphate isomerase
Structure of glyceraldehyde 3-phosphate dehydrogenase
Mechanism of glyceraldehyde 3-phosphate dehydrogenase
Diverse fates of pyruvate
Active site of alcohol dehydrogenase
NAD+ binding site of dehydrogenases
Gluconeogenesis
Pyruvate dehydrogenase complex (irreversible reaction)
Citrate synthase
Mechanism of Citrate synthase
Aconitase
Isocitrate dehydrogenase
a-Ketoglutarate dehydrogenase
Succinyl CoA synthetase
Succinate dehydrogenase
Fumarase
Malate dehydrogenase
Chemical and enzymatic syntheses
of glycosides and oligosaccharides
Most commonly used protecting groups in carbohydrate chemistry
Bn
O
BnCl, base
Bz
BzCl, base
Ac
Ac2O, Py
H2, Pd/C
NaOMe, MeOH
NH3/MeOH
O
O
O
NaOMe, MeOH
NH3/MeOH
O
O
O
O
O
isopropylidene
benzylidene
acetone, TsOH
CH3C(OCH3)2, TSOH
PhCH=O, ZnCl2
HCl, THF
HCl, THF
H2, Pd/C
Nucleophilic substitution of halogenases (Koenigs-Knorr)
OR'
R'O
R'O
O
OR'
OR'
OR'
HX
O
R'O
R'O
OH
+
X
OR'
OR'
X
X = Cl or Br
Nu
-
Nu-
SN2
OR'
OR'
R'O
R'O
O
R'O
R'O
O
Nu
OR'
R'O
R'O
O
OR'
Nu
Neighbouring group participation
OR'
-XO
R'O
R'O
OR'
OR'
X
O
O
R'O
R'O
O
O
R
O
R'O
R'O
O
O
O
Nu- R
R
OR'
HN
O
R
O
N
O
R'O
R'O
O
Nu
O
O
R
Trichloroacetimidate method
1. base
2. Cl3CN
OR'
R'O
R'O
O
OR'
OH
imidates
OR'
OR'
O
+
R'O
R'O
thermodynamic OR' O
R'O
R'O
kinetic
NH
O
O
OR'
NH
ROH,
acid
Cl3C
ROH, acid
OR'
OR'
R'O
R'O
O
OR
OR'
R'O
R'O
O
OR'
OR
CCl3
Scheme 1. (a) CH3COCl, CH2Cl2, Pyridine; (b) TMSOTf, CH2Cl2, -10 °C to room temperature (dry); (c) 90% TFA; then BzCl–
Pyridine; (d) 2% CH3COCl–CH3OH, 0 °C to room temperature; (e) PdCl2, 90% acetic acid–NaOAc, room temperature, 12 h; then
Cl3CN, DBU, CH2Cl2 2 h; (f) saturated NH3–MeOH, room temperature, 36 h; then H2O, room temperature, 5 h.
Thioglycoside/fluoride method
OR'
O
R'O
R'O
OR'
DAST/NBS
O
R'O
R'O
SPh
OR'
OR'
OR'
OR'
OR'
OR'
OR'
OR'
O
R'O
or NBS
R'O
or NIS/TfOH
or dimethyl(methylthio)sulfonium triflate
O
F
AgClO4, SnCl2
1. mCPBA
2. Tf2O
R'O
R'O
O
HO
R'O
OR'
O
R'O
OR'
OR'
ROH
R'O
R'O
O
OR'
O
OR
SPh
SPh
Scheme 2. a) Ac2O/pyridine (quant.); b) chloroacetic anhydride/pyridine, CH2Cl2 (93 %); c) HF/pyridine, NBS, CH2Cl2 (93 % 6),
(96 % 7); d) TMS-N3, BF3 OEt2, CH2Cl2 (91 % 8), (92 % 9); e) MeOH, dioxane, NaOMe (67 %); f) K2CO3, MeOH, CH2Cl2 (92 %);
g) BF3 OEt2, CH2Cl2 (83 %); h) BF3 OEt2, CH2Cl2 (86 %); i) K2CO3, MeOH, dioxane (79 %); k) K2CO3, MeOH, CH2Cl2 (94 %).
Reagents and conditions: (a) NIS, TMSOTf; 89.1% for 4; 65.5% for 15; (b) 90% TFA; 84.5% for 5; 63.7% for 6 (from 1); (c)
TMSOTf, CH2Cl2, 71.9% for 8; 71.2% for 13; (d) Ac2O, Pyr; (e) CAN, 3:4:3 Toluene MeCN–water; (f) Cl3CCN, DBU, 78.7% from 9.
Phosphite method
OR"
OR'
R'O
R'O
Cl
O
OR'
OH
P
OR"
EtN(i-Pr)2
OR'
R'O
R'O
OR'
O
OR'
OR"
P
OR"
O
HO
R'O
OR'
OMe
Lewis acid (I2, ZnCl2,
TMSOTf, BF3.Et2O)
OR'
R'O
R'O
OR'
O
OR'
O
R'O
O
OR'
OMe
Polymer supported synthesis
Polymer supported donor
L
L
O
RO
X
O
HO
RO
O
Y
O
O
RO
RO
Y
Polymer supported acceptor
L
L
O
RO
X
HO
RO
O
O
RO
Y
O
RO
O
Y
Enzymatic methods
Glycosyltransferases (transfer glycosyl residues from UDP to an acceptor)
HO OH
O +
HO
OH
HO
HO
OUDP
O
-1,4-galactosyl- HO OH
NHAc
OH transferase
OH
HO
HO
O
O
O
NHAc
OH
OH
OH
UDP = uridinediphosphate
Glycosidases (cleave glycosidic bonds)
HO OAc
O
HO OH
HO
O
O
HO
OH
NO2
HO OAc
HO OH
O
-galactosidase
HO
OH
O
O
Enzymatic synthesis with glycosynthases (mutated glycosidases lacking nucleophile)
Synthesis of hexasaccharides 1 and 2 by route 1. i), ii) phosphate buffer pH 7.0, CaCl2 0.1 mM, 35 °C; iii) Ac2O/pyridine, 24 h, RT
(80 % from 3); iv) MeONa/MeOH, 4 h, RT (90 %); v) 1 M HCl, 30 min, RT; vi) Ac2O/pyridine, 12 h, RT (75 % from 4); (vii)
MeONa/MeOH, 3 h, RT (90 %).
Wong, Ley