06 CARBOHYDRATE CHEMISTRY
SYNOPSIS AND KEY CONCEPTS
- "Open Chain" Carbohydrate
pentose, hexose, etc. aldose, ketose; chemistry of
the carbonyl group: via oxidation of aldoses to -onic acids and -aric acids; reduction;
hydrazone and osazone formation; thioacetal formation; homologation (ascent)
by the Kiliani method; degradation (descent) by the Weerman
method; structural correlations by these methods
of Carbohydrates - Hemiacetal Formation
- Mutarotation of D-glucose -
b pyranose and furanose forms in
equilibrium. Pyranose form is usually favoured with most hexoses.
- Glycoside Formation (Glycosidation)
under kinetic control both a and b
methyl furanosides are formed. Under thermodynamic control
the a pyranoside is the
major isomer. The anomeric effect is explained in terms of lone
pair-lone pair repulsion, dipole-dipole interactions and by M.O. theory.
Glycosides are stable in neutral or basic solution but readily
hydrolysed to the free sugar with dilute aqueous acid. Modern methods of
glycoside synthesis: trichloroacetimidate activation.
- Reactions of Carbohydrates - Selective hydroxyl protection and
neighbouring group participation
- Acetylation to give the a and b pyranose forms of the
penta- acetate; preparation of a-glycosyl halides and their conversion to
glycosides and formation of glycals; reactions of
glycals e.g. with dilute aqueous acid to give
2-deoxy-sugars and with peracids to give epoxides
- MeI/NaH methyl ethers - difficult to remove
- Benzyl ethers - cleaved by H2/Pd or
- Silyl ethers - volatile for mass spectral studies,
very readily cleaved by H3O+/or
KF/H2O, variable reactivity depending on
- Allyl ethers - acid stable, isomerisation with
or (Ph3P)3RhCl to give acid
labile vinyl ethers
- Triphenylmethyl ethers, "trityl" ethers -
selective for primary OH. Removed by dilute acid
- Acetal and ketal formation - ketones prefer to form 5 membered
ring ketals-1,2 diol protection. Aldehydes prefer to form 6
membered ring acetals-1,3 diol protection.
- Sulfonate esters - preparation and selectivity for primary
hydroxyl; intermolecular nucleophilic displacement reactions and
their problems; deoxygenation via free radical chain
reaction of xanthate esters with tri-n-buylstannane;
intramolecular nucleophilic displacement reactions give ethers
and epoxides (anhydro sugars); ring opening of epoxides and
- Keto sugars - best prepared by oxidation of alcohol with
DMSO/Ac2O or DMSO/P4O10;
nucleophilic attack from the least hindered side
- Unsaturated sugars - the Corey-Winter Olefin synthesis
(thiocarbonates + trimethyl phosphite); reduction of ditosylates
with sodium iodide and zinc
- Amino sugars - tosylate displacement with azide followed by
LiAlH4 reduction; epoxide ring opening by ammonia;
reduction of ketoximes with LiAlH4
- Use of Carbohydrates
- Aminoglycosides are important in antibiotics e.g. erythromycin,
For a review of the preparation and reaction of aminoglycosides see:
Topics in Antibiotic
Chemistry Vol 1, p 1; Sammes, P.G., Ed.; John Wiley and Sons,
- In non-carbohydrate natural product synthesis carbohydrates belong
to the "Chiral Pool" i.e. they are a very cheap source of
starting materials for organic synthesis which contain chiral
Hanessian, S. Acc. Chem. Res. 1979, 12, 159.
Fraser-Reid, B. Acc. Chem. Res. 1975, 8, 192.
Chemistry" Hough, L. and Richardson, A.C. in "Comprehensive Organic
Chemistry", Ed. Barton, D.H.R.; Ollis, W.D.; Haslam, E.; Pergamon Press, Oxford, 1979, vol. 5, p. 687-753.
Glycosides" Schmidt, R.R. in "Comprehensive Organic Synthesis",
Ed. Trost, B.M.; Fleming, I.; Winterfeldt, E.; Pergamon Press, Oxford, 1991, vol. 6, p. 33-64.
"Exploration with Sugars How
Sweet it Was" Lemieux, R.U. American
Chemical Society, Washington, D.C., 1990.
Chemistry" Kennedy, J.F. Claredon Press, Oxford, 1988.