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406 Carbohydrates

SCHEME 26 Biochemical synthesis of a trisaccharide using two enzymes, β-(1 → 4)-galactosyltransferase to form
the disaccharide and an α-(2 → 3)-sialytransferase to form the desired product.

having an acetyl group where the next monomer is to substrate acceptors. The above scheme illustrates the en-
be attached. Its reactive leaving group, the trichloroace- zymatic synthesis of a trisaccharide by using a β-(1 → 4)-
timidate, is replaced by the OH of MPEG-DOX to give galactosyltransferase to form a disaccharide and an
a blocked monomer-MPEG-DOX (B), which is treated α-(2 → 3)-sialytransferase to form the target trisaccharide
with base (DBU) to remove the acetyl (Ac) group and (see Scheme 26).
then with A to form a blocked dimer (C). Repetition of
theseoperationswillformthe deacetylatedblockedtrimer,
tetramer, and pentamer. When the desired number of 4. Reactions
monomers are linked together, the product is catalytically
Chemical modifications of oligosaccharides usually in-
hydrogenated to remove the benzyl blocking groups and
volve the reactive primary hydroxyl group, because se-
separate the oligosaccharide from the linker and polymer
lective blocking and deblocking of secondary hydroxyl
(MPEG-DOX). The pentasaccharide is separated at the
groups is considerably more difficult. As the DP of an
endofthesynthesisbyhydrogenation,whichalsoremoves
oligosaccharide increases, directing a substituent in a par-
the Bn blocking groups (see Scheme 25).
ticular moiety becomes more difficult. In a disaccharide,
it is possible to direct a substituent toward the terminal
(nonreducing) saccharide moiety by blocking the primary
3. Biochemical Synthesis of Oligosaccharides
hydroxyl group of the reducing moiety with a 1,6-anhydro
This method is particularly useful for the synthesis of com- ring. The latter is introduced by treatment of the disaccha-
plex oligosaccharides that exist in small amounts difficult ride glycoside (usually a phenyl glycoside) with base. Two
to characterize and study. Examples of these are the cell examples of selective reactions involving the terminal ring
surface oligosaccharides responsible for cell recognition. of a disaccharide are depicted in Scheme 27.
The most commonly used enzymes are glycosidases and
glycosyltransferases, or a combination of both. The gly- 1. The introduction of a carboxylic group by oxidation
cosidases are hydrolytic enzymes that can used for syn- of the primary hydroxyl group of β-benzyl
thesis by carrying out the reaction in the reverse direction. cellobioside with oxygen in the presence of palladium
Glycosyltransferases are enzymes that catalyze the syn- on charcoal occurs preferentially at the terminal ring.
thesis of glycosides and oligosaccharides by the transfer However, greater selectivity can be reached if the
of monosaccharides from nucleotide donors to specific 1,6-anhydro derivative is first formed.