Anomerization process

A useful extension of the in situ anomerization process involves the employment of C-nucleophiles such as vinyl and allyl magnesium bromides. Grignard reactions to per-O-benzylated glycosyl iodides proceed stereoselectively when a strong nucleophile like allyl magnesium bromide is used, giving [1-C-allyl fucosides (95% P-only)... 

Mechanistic studies [123] have shown that thioglycosides can undergo in situ anomerization in the presence of iodonium ion catalysts. It has been demonstrated that this anomerization proceeds by intermolecular exchange of alkyl thio groups. An increase in the steric bulk of the leaving group resulted in incomplete or no anomerization. It has been proposed that this anomerization process is important for the stereochemical outcome of glycosylations [123]. 

The optical rotations just cited for each isomer are those measured immediately after each one is dissolved m water On standing the rotation of the solution containing the a isomer decreases from +112 2° to +52 5° the rotation of the solution of the p isomer increases from +18 7° to the same value of +52 5° This phenomenon is called mutarotation What is happening is that each solution initially containing only one anomeric form undergoes equilibration to the same mixture of a and p pyranose forms The open chain form is an intermediate m the process... 

The /7-nitrophenyl ether was used for the protection of the anomeric position of a pyranoside. It is installed using the Konigs-Knorr process and can be cleaved by hydrogenolysis (Pd/C, H2, AC2O), followed by oxidation with ceric ammonium nitrate (81-99% yield). ... 

Bu2SnO, benzene BnBr, DMF, heat, 80% yield. This method has also been used to protect selectively the anomeric hydroxyl in a carbohydrate derivative. The replacement of Bu2SnO with Bu2Sn(OMe)2 improves the process procedurally. The use of stannylene acetals for the regioselective manipulation of hydroxyl groups has been reviewed. ... 

If it is assumed that the Mitsunobu glycosidation reaction described above proceeds through an SN2-type process with inversion of configuration at the anomeric position, then it follows that the desired / -glycoside can be formed selectively if pure a-lactol 17 is used in the reaction. Unfortunately, the /Mactol isomer of 17 is thermodynamically more stable than the a-diastereoisomer and is formed almost exclusively if the system is allowed to fully equilibrate. In the protic medium used for the Luche reduction, a signifi-... 

The isomerism existing between the pairs of nucleotides was attributed to the different locations of the phosphoryl residues in the carbohydrate part of the parent nucleoside,49 63 since, for instance, the isomeric adenylic acids are both hydrolyzed by acids to adenine, and by alkalis or kidney phosphatase to adenosine. Neither is identical with adenosine 5-phosphate since they are not deaminated by adenylic-acid deaminase,68 60 and are both more labile to acids than is muscle adenylic acid. An alternative explanation of the isomerism was put forward by Doherty.61 He was able, by a process of transglycosidation, to convert adenylic acids a" and 6 to benzyl D-riboside phosphates which were then hydrogenated to optically inactive ribitol phosphates. He concluded from this that both isomers are 3-phosphates and that the isomerism is due to different configurations at the anomeric position. This evidence is, however, open to the same criticism detailed above in connection with the work of Levene and coworkers. Further work has amply justified the original conclusion regarding the nature of the isomerism, since it has been found that, in all four cases, a and 6 isomers give rise to the same nucleoside on enzymic hydrolysis.62 62 63 It was therefore evident that the isomeric nucleotides are 2- and 3-phosphates, since they are demonstrably different from the known 5-phosphates. The decision as to which of the pair is the 2- and which the 3-phosphate proved to be a difficult one. The problem is complicated by the fact that the a and b" nucleotides are readily interconvertible.64,64... 

These results clearly indicate that barriers to all isomerisation processes are at least less than about 8kcalmol 1. In /V-benzyloxy-7V-chlorobenzamide 44 the amide isomerisation was not observable but the anomeric overlap resulted in diastereotopic benzylic hydrogens, which at coalescence afforded a barrier for rotation about the N-OBn bond of around 10.3 kcalmol-1.32 Like its /V-chloro analogue, the amide isomerisation barrier in 43 is too low to be observed by 3H NMR and even though there is definitive X-ray and theoretical evidence for anomeric effects in /V-acyloxy-/Y-alkoxyamidcs, the barrier to isomerisation about the N-OBn bond must be lower than 10.3 kcalmol-1. The n0-CN ci anomeric interaction in 44 is predicted to be stronger than the n0-CN OAc interaction in 43 on purturbation arguments.32... 

Ar-Acyl oxy- A -a 1 k oxyamides have been found to undergo SN2 reactions with a number of organic and inorganic nucleophiles including anilines, thiols, hydroxide and azide anions. Reaction products from all of these processes are themselves reactive anomeric amides and outcomes have uncovered novel chemistry of this unusual class of compounds. 

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