Page 56 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

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Encyclopedia of Physical Science and Technology EN006P-81 June 29, 2001 23:54

840 Glycoconjugates and Carbohydrates

3. Reactions at Secondary Hydroxyls CH 2 OH OCH 2
Me 2 C
H O H OCH O H
Substitution reactions at secondary hydroxyls are gener- Me 2 CO
H OH H
ally performed either for analysis of structure or to serve a OH H ZnCl 2 , H 3 PO 4
HO OH H O
protective function during other reactions. Etherification
H OH H O CMe 2
of the nonanomeric hydroxyls was an important structural
tool in the analysis of oligosaccharide and polysaccharide FIGURE 14 1,2 5,6-diisopropylidene D-glucofuranose. Formed
by reaction of D-glucose with acetone in the presence of a suitable
structure. Methyl ethers have been employed for struc-
catalyst. The furanose product dominates due to kinetic control of
tural determination for more than 75 years. Thus, methyl the reaction.
ether formation in a polysaccharide results in substitu-
tion only at free hydroxyls. Subsequent analysis of the
acetals or ketals and of a group of interactions restricted
methylated derivatives reveals positions previously occu-
to hydroxyls on adjacent carbons.
pied in glycosidic linkage. Reagents used for this purpose
Reaction of glucose with acetone results in the forma-
have evolved from dimethylsulfate to the commonly em-
tion of 1,2 5,6-diisopropylidene glucofuranose (Fig. 14).
ployed method of Hakomori using sodium hydride and
The furanose product arises because of the high reactivity
dimethylsulfoxide.
of the exocyclic hydroxymethyl group thus favoring the
Another frequently used ether substituent is the benzyl
formation of the five-membered ring. This is a commonly
group, which is stable under a variety of reaction condi-
used protective scheme since the ketal function is readily
tions but can be removed by catalytic hydrogenation. This
cleaved by mild acid; in fact, selective cleavage of the 5,6
is employed mainly during synthetic schemes where pro-
ketal can be accomplished. Acetals are likewise formed;
tection of specific hydroxyls is required. Currently, ether
reaction of glucose with benzaldehyde results in formation
formation is used primarily as an adjunct to mass spectro-
of the 4,6 benzylidene derivative, another useful synthetic
metric analysis.
intermediate.
The secondary hydroxyl groups can also be esterified.
Adjacent hydroxyls that are cis can undergo several dif-
Acetyl substitution via acetic anhydride is often used, es-
ferent reactions. Included in this group is complexation
pecially as a protective group. Tosyl substitution using
with borate to form a transient cyclic adduct (Fig. 15).
toluenesulfonyl chloride is often employed since the prop-
This alters chemical reactivity and electrophoretic prop-
erties of that ester (good leaving group) allow for SN 2
erties of the reactive sugar and has several applications.
displacement resulting in inversion of configuration. Ac-
A key property of cis-hydroxyls is their susceptibility
etate esters are readily removed under basic conditions
to carbon–carbon bond cleavage by metaperiodate. This
(methoxide ion) when glycosides remain intact.
oxidative reaction proceeds via a five-membered ring in-
termediate, generates a pair of aldehydes, and results in
4. Reactions at the Hydroxymethyl Group scission of the carbon chain (Fig. 16). It has been demon-
strated that the cis orientation is necessary for this reaction
The exocyclic nature of this group makes it the second since fixed ring structures with trans-hydroxyls do not re-
mostreactiveofthehydroxylfunctions.Tritylationisoften act. The reaction has been utilized to identify saccharides
employed to transiently block C-6 (ready removal under in tissues via subsequent treatment of the generated alde-
mild acid conditions). This is also the site of enzymatically hydes with a suitable amine, forming a colored Schiff base
catalyzed phosphorylation of glucose and other sugars, the product (periodate-Schiff reaction).
first step in their metabolic utilization. Oxidation to a car-
boxylic acid is common. The resulting uronic acid is, for
the common sugars, widely distributed in natural polysac- C. Biosynthesis
charides in both plants and animals. It is of interest that
The fixation of carbon dioxide via photosynthesis is the
L-iduronic acid (the 5-epimer of D-glucuronic acid) and
initiating reaction in saccharide synthesis in nature. Light
L-guturonic acid (the 5-epimer of D-mannuronic acid) are
formed in nature after the respective precursor uronic acid
has been incorporated into polymeric linkage. HO OH HO HO O
B R B R H 2 O
5. Hydroxyl Pairs HO OH HO HO O
FIGURE 15 Borate ester formation. cis-Hydroxyls are preferred.
The proximity and defined stereochemistry of hydroxyl
The extent of reaction was originally monitored by following the
groups in the ring structures of saccharides allows for a change in conductivity of borate solutions on the addition of
number of selective reactions. These include formation of saccharide.