Anomerization Reactions

Absence of Rate-Limiting Anomerization Reactions in Glucose Metabolism... 

This at least partly offsets the expected rate enhancement which should result from increasing the rate of anomerization (reaction 3, Figure 1). Thus the two factors that favor high stereoselectivity may favor low rates in this reaction. 

Although not strictly sugars, polyhydroxylated carbocylic rings have many of the non-anomeric reactions of carbohydrates proper, and because of the... 

The half-life for nonenzymic interconversion of the anomers is about 0.4 sec. Stopped-flow kinetic measurements, using the isomerase from yeast, indicate that both the a- and j8-anomers of glucose 6-phosphate are used directly by the enzyme to give the a- and )8-anomers of fructose 6-phosphate, although the a-anomer is consumed at least 20-fold faster than the )3-anomer. In addition, the enzyme is capable of catalyzing the interconversion (anomerization) of the a-and jS-anomers. With the a-anomer of glucose 6-phosphate, the anomerization reaction is approximately twice as fast as the isomerization reaction. 

Self-anomerization reaction (3) with fully protected deoxycytidine lb is readily scaled up, and the corresponding a-anomer 2b is crystallized from toluene and then treated with 0.19M sodium hydroxide at 0°C for 5 min. After neutralization with Dowex 50W (pyridinium form), 4-A -benzoyl-a-deoxycytidine (2l2) is obtained as colorless crystals in 44% overall yield. 

Mannosides are difficult to obtain since here a 2-O-acyl group blocks the -position. 2-O-Benzyl-a-mannosyl bromides give, however, high yields of pure -glycosides with a heterogeneous silver silicate catalyst preventing anomerization and SnI reaction of the bromide H. Paulsen, 1981 B, Q. 

Imidazole can be A -allylated. The A -glycosylimidazole 299 is prepared by regiospecific amination at the anomeric center with retention of configuration. Phenoxy is a good leaving group in this reaction[181]. Heterocyclic amines such as the purine base 300 are easily allylatedfl 82]. 

This reaction has been used m an imaginative way to determine the ring size of glycosides Once all the free hydroxyl groups of a glycoside have been methylated the glycoside is subjected to acid catalyzed hydrolysis Only the anomeric methoxy group IS hydrolyzed under these conditions—another example of the ease of carbocation for matron at the anomeric position... 

When a preparative method for an aldonic acid is re quired bromine oxidation is used The aldonic acid is formed as its lactone More properly described as a reaction of the anomeric hy droxyl group than of a free aldehyde... 

Ph3C BF, CH2CI2 or CH3CN, H2O. In this case the reaction with DDQ failed to go to completion. This was attributed to the reduced electron density on the aromatic ring because of its attachment at the more electron-poor anomeric center. 

A point to be emphasized about glycoside fonnation is that, despite the presence of a number of other hydroxyl groups in the carbohydrate, only the anomeric hydroxyl group is replaced. This is because a carbocation at the anomeric position is stabilized by the ring oxygen and is the only one capable of being fomned under the reaction conditions. 

This ether, developed for the protection of a pyranoside anomeric hydroxyl, is prepared via a Konigs-Knorr reaction from the glycosyl bromide and 2-(ben-zylthio)ethanol in the presence of DIPEA. It is cleaved, after oxidation with dimethyldioxirane, by treatment with LDA or MeONa. ... 

Note the preferential reaction at the anomeric hydroxyl. The method is also effective for the protection of primary and secondary alcohols. 

When the reaction was run in CH3CN, migration of the EtS group to the 2-position was observed. This is attributed to episulfonium salt formation, with the resultant addition of acetate at the anomeric position. ... 

The Mitsunobu reaction is usually used to introduce an ester with inversion of configuration. The use of this methodology on an anomeric hydroxyl was found to give only the /3-benzoate, whereas other methods gave mixtures of anomers. Improved yields are obtained in the Mitsunobu esterification when p-nitrobenzoic acid is used as the nucleophile/ Bis(dimethylamino) azodicarboxylate as an activating agent was... 

Patemo-Biichi reaction between 2-methylfuran 31 and an a-hydroxyaldehyde 30 to form the core oxetane. Two of the three stereocenters set in the electrocyclization appear in the final product while the third is selectively reversed with anomeric assistance. 

Reaction of 3-amino-1-propanol and 5-bromo-5-deoxy-D-furanoxylose (25) in D2O was monitored by NMR (Scheme 4). The a-anomer of trihydroxypyridoPd-f l-LbSloxazine 26 formed 20 times faster, but the /3-anomer 27 was more stable (A / 7.3). The faster formation of the Q -anomer is a consequence of a kinetic anomeric effect that destabilizes the transition state for equatorial A -alkylation and formation of the /3-anomer 27 (OOJOC889). 

Reaction of 3-aminopropanol with an a and [3 mixture of 5-bromo-5-deoxy-2-xylofuranose (25) and 5-(9-tosyl-D-lyxofuranose in MeCN afforded anomeric mixtures of trihydroxypyrido[2,l-Zi]l,3]oxazines 20, 21 and 22-24, respectively (99T6759, 99T14251). 

A more complicated reaction sequence has been used by Ukita and Nagasawa (59) in their synthesis of 2-deoxy D-ribose 5-phosphate (2-deoxy D-erythro-pentose 5-(dihydrogen phosphate)), (29). They phosphorylated a mixture of the anomeric methyl deoxyribofuranosides (24)... 

We saw in Section 25.6 that reaction of a monosaccharide with an alcohol yields a glycoside in which the anomeric -OH group is replaced by an -OR substituent. If the alcohol is itself a sugar, the glycosidic product is a disaccharide. 

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