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

390 Carbohydrates

alkyl glycosides, discussed earlier, which possess acetal- c. Anhydrides and disaccharides. An intra or in-
type OR groups. Methyl ethers have been used exten- termolecular nucleophilic attack initiated by the oxygen
sively in the structure elucidation of saccharides. They atom of a suitably placed hydroxyl group on the anomeric
were first used by Haworth to determine the ring size of carbon atom of the same or a different sugar will afford
monosaccharides and the ring size and position of linkage an anhydride or a disaccharide, respectively. The reaction
of oligosaccharides. More recently, they have been used is best performed by introducing a good leaving group,
to volatilize monosaccharides before they are subjected to usually a halogen atom, on the anomeric carbon atom
gas-chromotographic analysis. Because silyl derivatives and blocking all of the hydroxyl groups except the one to
are easier to prepare than methyl ethers, the former have be involved in the subsequent reaction (see Scheme 17).
now replaced methyl ethers in the gas-chromatographic In this way, the formation of undesired products can be
analysis of monosaccharides. On the other hand, because avoided.
methyl ethers are stable toward acid- and base-catalyzed Disaccharides are often obtained enzymatically, by
hydrolysis, they continue to be used as a means of la- passing the substrate or substrates (the saccharides in-
beling free hydroxyl groups in saccharides, a procedure volved in the dimerization) through a column filled with
frequently used in the structure elucidation of oligosac- a polymer that had been prebound chemically to the spe-
charides and polysaccharides. It is for this reason that the cific enzyme needed to perform the transformation. This
problem of permethylating saccharides (etherifying all of method has, of late, acquired attention in industrial op-
their hydroxyl groups) continues to attract the attention erations, because it allows the enzymes to remain active
of carbohydrate chemists. The original methods of Purdie indefinitelyonthecolumnandpreventstheirbeingwashed
(MeI and AgOH) and of Haworth (Me 2 SO 4 in alkali) have away during the work-up.
been much improved by the use of such aprotic solvents as
HCONMe 2 (DMF) or Me 2 SO (DMSO). Today, the most d. Cyclic acetals. If oriented properly, any two adja-
widely used methylating procedure is that of Hakomori, cent (but not necessarily contiguous) hydroxyl groups will
who used sodium hydride and Me 2 SO to generate the base reactwithanappropriatealdehydeorketonetoyieldanun-
−
MeSOCH needed for this type of methylation. strained five- or six-membered cyclic acetal, respectively.
2
Benzyl ethers offer unique advantages in syntheses re- The most commonly used carbonyl compounds are ben-
quiring the selective blocking and deblocking of hydroxyl zaldehyde, which affords mostly six-membered benzyli-
groups. They can be introduced under mild conditions dene acetals, and acetone, which yields five-membered
by the action of benzyl chloride in pyridine and can be isopropylidene acetals. The latter derivatives have the ad-
removed in neutral media by catalytic hydrogenolysis, vantage of existing in one isomeric form, unlike benzyli-
which does not affect esters or cyclic acetals. The for- dene derivatives, which exist in two isomeric forms. This
mer class of compounds is base labile, and the latter, acid is because, on reacting with chiral glycols, all aldehydes,
labile. except formaldehyde, and all mixed ketones yield chiral
Other synthetically useful ethers are the triphenyl- acetals.
methyl ethers, or as they are often called, trityl deriva- The formation of cyclic acetals is catalyzed by acids
tives (Ph 3 C ). Their bulky phenyl groups render their and proceeds by two successive nucleophilic attacks; at
formation from secondary and tertiary hydroxyl groups first one hydroxyl group attacks the protonated carbonyl
so difficult that they are normally obtained from primary derivative to form the hemiacetal. The latter, in turn, be-
hydroxyl groups only. These ethers are therefore used to comes protonated and is attacked by the second hydroxyl
block the primary hydroxyl groups selectively, so as to group.
leave the secondary hydroxyl groups free for subsequent The formation of isopropylidene acetals can be
reactions. Removal of the trityl ethers is very facile and can achieved by treatment of a saccharide derivative with ace-
be achieved by mild acid hydrolysis. Such organic acids as tone or its dimethyl acetal (2,2-dimethoxypropane) in the
acetic acid, which do not affect esters or cyclic acetals, se- presence of an acid catalyst such as HCl or H 2 SO 4 and
lectively deblock the oxygen atom bearing the trityl group a dehydrating agent. The reaction is often conducted at
1
and regenerate the primary hydroxyl group, with libera- room temperature and can be monitored by H NMR spec-
tion of triphenylmethanol. Alternatively, the trityl ether troscopy. The signals of two methyl groups are usually
group can be removed by catalytic hydrogenolysis, which well resolved because of their chiral environment.
then affords triphenylmethane and the free primary hy- A useful starting material in many syntheses
droxyl group. The ease of hydrolysis of trityl ethers may is 1,2 : 5,6-di-O-isopropylidene-α-D-glucofuranose, ob-
sometimes be responsible for the occurrence of undesir- tained by treating D-glucose with acetone. This derivative
able hydrolysis during the course of a subsequent reaction, affords an easy means of access to furanoses having a free
particularly when vigorous conditions are used. hydroxyl group on C-3.