Page 96 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Encyclopedia of Physical Science and Technology EN002C-80 May 25, 2001 20:18

404 Carbohydrates

Consider now the synthesis of raffinose, which is O- Although it is possible to achieve the synthesis of higher
α-D-galactopyranosyl-(1 → 6)-O-α-D-glucopyranosyl- oligosaccharides by the addition of one monosaccharide
(1 → 2) β-D-fructofuranoside. It is evident that the at a time, it is advantageous to add the oligosaccharide
galactopyranosyl halide needed for this synthesis must be components of a large oligomer in blocks of two or more
protected by a nonparticipating group in order to afford the monosaccharides (block synthesis). Thus, the trisaccha-
desired α-D-galactopyranosyl linkage (cis-1,2 configura- ride and tetrasaccharide can be prepared by reacting a
tion). Furthermore, since the adduct (sucrose) is a nonre- disaccharide glycosyl halide with a suitably protected
ducing disaccharide that possesses three primary hydroxyl mono- or disaccharide. It is evident that a second round
groups (all of which are available for attack on the carbo- of reactions would afford penta- and hexasaccharides.
nium ion), it is necessary to block at least two of them to Another interesting approach to the chemical and enzy-
ensure that the desired primary hydroxyl group, namely, matic synthesis of oligosaccharide is the use of a stationary
the one attached to C-6 of the glucopyranose moiety, is polymer support to retain substrates (or enzymes) inside a
the one that reacts with the galactopyranosyl halide. Ex- reactor (usually a column), while successive reagents are
perimentally, raffinose was synthesized by reacting, un- passed through the polymer and are then washed out of the
der Koenigs–Knorr conditions, a benzyl-protected galac- reactor. The advantage of this method is that it affords an
topyranosyl halide (tetra-O-benzyl-α-D-galactopyranosyl efficient way of carrying out successive reactions without

chloride) with a sucrose derivative (2,3,4,1 ,3 ,4 ,6 -hepta- loss of the material attached to the column. For industrial
O-acetylsucrose) having ester groups replacing all hy- enzymatic reactions involving costly enzymes, retaining
droxyl groups except OH-6 of the glucopyranose moiety these inside the reactor would seem quite attractive.
(see Scheme 24).
2. Synthesis of Oligosaccharides on Fixed Beds
of Polymers
The importance of glycopeptides and glycolipids in
medicine and the small amount of oligosaccharides re-
leased from natural sources necessitated the development
of improved methods to prepare them including novel ap-
proaches in their synthesis. As in the case of automatic
nucleotide- and peptide-synthesizers, a serious search has
been made to develop suitable polymers for use as fixed
beds and as linkers to attach saccharides and to facilitate
the removal of the oligosaccharide formed at the end of
the synthesis from the polymer support. The successive
monomers are added one at a time to the linker until the
desired oligomer is formed, then it is separated from the
linker. Many oligosaccharide syntheses on polymer sup-
portusethecommerciallyavailablepolymer,polyethylene
ω-monomethyl ether (MPEG) attached to the linker, α,α-
dioxyxylyl diether (DOX). The product, (MPEG-DOX),
needed for the oligosaccharide synthesis on solid support
is prepared as follows:

Me-O-(CH 2 -CH 2 ) n -CH 2 -CH 2 -OH + Cl-CH 2 -(C 6 H 4 )-CH 2 -CL →
(MPEG)
Me-O-(CH 2 -CH 2 ) n -CH 2 -CH 2 -O-CH 2 -(C 6 H 4 )-CH 2 -Cl →
Me-O-(CH 2 -CH 2 ) n -CH 2 -CH 2 -O-CH 2 -(C 6 H 4 )-CH 2 -OH

(MPEG-DOX)
Scheme 25 illustrates the use of MPEG-DOX in the
synthesis of a pentasaccharide. The first monosaccha-
SCHEME 24 Synthesis of raffinose. ride added (A) is a benzyl blocked trichloroacetimidate