Nucleosides anomeric configuration

David and Lubineau191 reported the synthesis of pseudocytidine [5-/3-D-ribofuranosylcytosine (270)] and its a anomer by a procedure analogous to that used in preparing pseudouridine.155-157 Thus, 2,4 3,5-di-O-benzylidene-a/de/iydo-D-ribose (223) was condensed with the dilithio derivative of 2-0,4-N-(trimethylsilyl)cytosine, and the resulting, epimeric, acyclic derivatives were subjected to acid-catalyzed cyclization. The anomeric configuration of the free C-nucleosides was ascertained by spectroscopic methods and by their transformation into a- and /3-pseudouridine in the presence of nitrous acid. The anomeric 5-(/3-D-ribofuranosyl)isocytosines have also been prepared by Fox and coworkers.1913... 

The correct anomeric configuration of the a-D-glucopyranosyl pyrophosphate ester is essential (the /3-D-glucopyranosyl ester does not react),342 but the exact distance between the nucleoside moiety and the glycosyl group seems to be a less critical factor. Thus, the phosphonate analog 67 can serve as a substrate.210... 

N-Alkylation in the azine ring is demonstrated by the preparation of 2-substituted 6-(jS-D-ribofuranosyl)oxazolo[5,4-rf]pyrimidin-7(6/T)-ones (181). In this case the silyl ether variant of the Hilbert-Johnson method for the synthesis of pyrimidine nucleosides has been used the pyrimidinone (180) is converted into its silyl ether using HMDS and the ether reacted with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide under Hg(II) catalysis. Deacetylation using methanolic ammonia gives the nucleoside with a /3-anomeric configuration (74JMC1282). 

NMR studies on purine nucleosides have been undertaken to assign the site of glycosylation, to determine the anomeric Configuration, to elucidate the sugar puckering and to determine the synjanti ratio of the location of the bases. Rare tautomeric forms and protonation sites were also studied. 

Two studies of ORD on pyrimidine nucleosides have appeared which assist in the assignment of the anomeric configuration.The anomeric configuration can be assigned utilizing an NMR technique which compares the pyrimidine nucleoside with its 5,6-dihydroderivative. ... 

A growing number of coenzyme analogs have been prepared containing modifications in the nicotinamide sugar moiety. These modifications focus on three primary interactions inductive effects, tolerance of sugar substituents (anomeric configuration), and nucleoside flexibility (the importance of an intact furanose... 

Accepting the above structures, the transfer of monosaccharide residues from nucleoside pyrophosphate derivatives to phenolic hydroxyl groups appears to result in inversion of the anomeric configuration of the glycosyl residue.i 2> This is most certainly true of the formation of aryl... 

Enzymatic approaches to glycoside synthesis may circumvent these problems. Enzymes (i.e. nucleoside glycosyl transferases) are stereospecific and regioselective catalyzing glycosyl transfer reaction under mild conditions. Extensive protection-deprotection schemes are unnecessary and the control of anomeric configuration is managed. 

In a similar way, reaction of methyl 2-aminohept-2-ulofuranosate 165 [175] with acylated /J-o-glucopyranosyl or /i-D-ribofuranosyl isothiocyanates resulted in spirohydantoins 166 or 167 (Scheme 36), in almost quantitative yield [154], It is remarkable that, although both anomers of 165 are in equi-Ubrium under the reaction conditions, only spironucleosides of anomeric configuration were formed. Compoimds 166 and 167 can be considered simultaneously M-nucleosides and spironucleosides. 

Methods for determining the anomeric configurations of ribonucleosides have been reviewed. The well known anomeric-proton rule for determining anomeric configuration from n.m.r. chemical shifts has been supplemented by the rule, which states that the heterocyclic proton on the carbon next to the glycosidically linked nitrogen is downfield in the isomer in which the base and the C-l hydroxy-group are trans to each other relative to the same proton in the cis isomer. The rule holds for unprotected and acetalated nucleosides, but not for acyl or benzyl derivatives. ... 

It was reported that a nucleophile attacked the C2 position of the 2 -enesulfone nucleoside exclusively from the a-face of the pent-2 -enofuranosyl moiety of a P-nucleoside [17, 18]. This observation led to a study of the effect of the anomeric configuration on the stereochemical outcome of the addition of nucleophiles to vinyl sulfone-modified carbohydrates (Fig. 8.15). 

On the basis of semiempirical molecular modelling data, the total unreactivity of the primary alcohol group in l-(l-deoxy-P-D-psicofuranosyl)thymine (3) has been ascribed to hydrogen bonding with the base moiety as shown. The H- and C-n.m.r. spectra of ribofliranose in D2O have been fully assigned by use of 2D techniques. The C-n.m.r. spectra of methyl tri-O-acetyl-a- and -P-L-arabinofuranosides are referred to in Part 4 below, 2D H NOESY techniques were used to ascertain the anomeric configuration of several purine deoxyribonucleosides and the chemical shift values allowed differentiation between 7- and 9-A linked isomers. The anomeric configurations of the C-nucleosides 4, obtained in... 

Rearrangement by a 1,3-intramolecular shift from JV to occurs with retention of anomeric configuration in the nucleoside (113) during heating and g.c.-m.s. "... 

C N.m.r. has been used to distinguish between 7- and 9-purine substitution in ribofuranosyl nucleosides useful signals are those of C-1 which differ for the two types and those of the carbon atoms of the purine moiety which are characteristic for the two types of substitution. The anomeric configuration of mycosamine in the polyene antifungal antibiotics lucensomycin and nystatin has been determined by C n.m.r. the former contains an a-mycosaminyl residue while the latter is a j8-mycosaminide. ... 

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