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 proteinsFacilitate cell- cell contact

Carbohydrade Recognition at Infection Site

                                                                                                                        

Development of carbohydrate-based vaccines

Glycogen

Metabolism of carbohydrates

Glycogen phosphorylase

-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

-Ketoglutarate dehydrogenase

Succinyl CoA synthetase

Succinate dehydrogenase

Fumarase

Malate dehydrogenase

Chemical and enzymatic syntheses of glycosides and oligosaccharides

O Bn BnCl, base H2, Pd/C

O

O

Bz BzCl, base NaOMe, MeOHNH3/MeOH

O

O

Ac Ac2O, Py NaOMe, MeOHNH3/MeOH

O Oisopropylidene acetone, TsOH

CH3C(OCH3)2, TSOHHCl, THF

O O benzylidene PhCH=O, ZnCl2 HCl, THFH2, Pd/C

Most commonly used protecting groups in carbohydrate chemistry

OR'OR'O

OR'

OR'

OH

HX

OR'OR'O

OR'

OR'

Nu

OR'OR'O

OR'

OR'

X

OR'OR'O

OR'

OR'

Nu

OR'OR'O

OR'

OR'

X+

X = Cl or Br

Nu- Nu-SN2

Nucleophilic substitution of halogenases (Koenigs-Knorr)

OR'OR'O

O

OR'

X

-X-

OR'OR'O

OR'

Nu

Nu-

O

R

OR'OR'O

O

OR'

O

R

OR'OR'O

O

OR'

O

R

OO

R

HNO

R

N OO

Neighbouring group participation

OR'OR'O

OR'

OR'

OH

OR'OR'O

OR'

OR'

OR

OR'OR'O

OR'

OR'

Cl3CNH

OR'OR'O

OR'

OR'

OR

OR'OR'O

OR'

OR' NH

CCl3+

ROH, acid

1. base2. Cl3CN

ROH, acid

thermodynamic kinetic

imidates

O

O

Trichloroacetimidate method

                                                                             

          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.

OR'OR'O

OR'

OR'

SPh

DAST/NBSOR'O

R'OOR'

OR'

FOHO

R'OOR'

OR'

SPh

OR'OR'O

OR'

OR'

OOR'O

OR'

OR'

SPh

AgClO4, SnCl2

Thioglycoside/fluoride method

OR'OR'O

OR'

OR'

ROH OR'OR'O

OR'

OR'

OR

1. mCPBA2. Tf2O

or NBSor NIS/TfOHor dimethyl(methylthio)sulfonium triflate

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.

OR'OR'O

OR'

OR'

OH

Cl POR"

OR"

EtN(i-Pr)2

OR'OR'O

OR'

OR'

POR"

OR"

OR'OR'O

OR'

OR'

OOR'O

OR'

OR'

OMe

OHOR'O

OR'

OR'

OMe

Lewis acid (I2, ZnCl2, TMSOTf, BF3.Et2O)

Phosphite method

O

L

X

O

Y

HORO

O

XRO

RORO

RO

L

O

Y

HORO

O

L

O

Y

O

OL

O

Y

O

RO

RO

Polymer supported donor

Polymer supported acceptor

Polymer supported synthesis

O

HO

HOOH

OH

OUDP

OHNHAc

OHO

HO

OHO

HO

HOOH

OHOH

NHAc

OO

HO

OH

-1,4-galactosyl-transferase

Glycosyltransferases (transfer glycosyl residues from UDP to an acceptor)

+

UDP = uridinediphosphate

Enzymatic methods

O

HO

HOOH

OH

O NO2

OHO

HO

OAc

O

HO

HOOH

OHO

HO

O

OAc

Glycosidases (cleave glycosidic bonds)

-galactosidase

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 %).

Enzymatic synthesis with glycosynthases (mutated glycosidases lacking nucleophile)

Wong, Ley