Conformation glycals

The importance of substituent and conformational effects in glycal additions was also demonstrated in attempting Michael addition of an alkoxide to the O-linked 2-nitrogalactal 1S3 and its C-linked analog 154. The a-toio-isomer 156 was obtained from 154 in contrast to the result of Michael addition to the analogous O-linked disaccharide 153, which eventually gave the 2-acetamido-a-galactoside-terminated disaccharide 155. 

More recently McDonald et al. reported a rare example of 7-membered oxacyde formation based on the same concept [21]. Thus, polyoxygenated terminal alkynes 60 containing the dioxolane structure in the tether gave 7-endo cyclized glycals 61 in good yield. It is necessary to have the dioxolane ring in the tether for efficient reaction, probably favoring the suitable conformation for cyclization (Scheme 5.21). 

In recent studies, acceptable yields of (3-configurated 2-deoxy glycosides by application of the NIS reaction to uronic ester glycals like 38 have been reported [19]. By NMR studies the equilibrium conformation of the glycal 38 is shown to be shifted towards the inverted half-chair or half-boat conformation [5H4(D)]. 

Owing to the Curtin-Hammett principle, the ratio of the iodonium intermediates 39 and 40 does not reflect the distribution of the conformers in 38 (5H4 4H5 = 95 5). Thus, both the 2-deoxy-2-iodo-ot-mannoside 50 and the 2-deoxy-2-iodo-P-glucoside 51 are formed in almost equimolar amounts. Similar results are observed in glycals with nitrile or carboxamide functions [11]. 

Thiem and Ossowski79 considered that the conformation of the starting glycal was critical to the configuration of the product obtained. It was reasoned that 45... 

In the previous subsection, it was shown that the Ferrier reaction offers an opportunity to convert glycal derivatives into unsaturated sugar derivatives, which have an isolated double bond between C(2) and C(3). The Tipson-Cohcn reaction is another important reaction for the introduction of isolated double bonds.29 In this procedure, a cis or tram diols are converted into disulfonates (mesylates or tosylates) which are reductively eliminated with sodium iodide and zinc in refluxing DMF (Scheme 3.6a). In this reaction, the C(3) sulfonate is substituted by an iodide, which then is reductively removed by zinc with concomitant elimination of the second sulfonate moiety, introducing a double bond. Stereoelectronic effects make nucleophilic substitutions at C(3) more favourable than similar reactions at C(2) (see Section 3.2.3). Probably, the elimination proceeds through a boat conformation. In this case, the iodide and tosylate are in a syn relation. In most cases, E2 elimination proceeds via a transition state involving an anti orientation. Nevertheless, syn elimination becomes the dominant mode of reaction when structural features prohibit an anti orientation. 

On the other hand, in the case of pentopyranose, the 1,4-anfi-adduct was preferentially obtained (O Scheme 29), due to the preferred conformation of the intermediate oxonium cation derived from the glycal [46,51a]. 

Optical rotatory dispersion studies have been carried out on the glycals, and it has been pointed out that D-xylal ([a]D — 254°) and D-arabinal ([a]D + 196°) conform with the observation that allylic cyclohexenols of the configuration (60) are more dextrorotatory than their epimers. This also conforms with the wider generalizations of Bose and Chatterjee. On ascending paper-chromatograms developed with 4 1 5 1-butanol-acetic acid-water, the Rp values of D-glucal, D-galactal, and D-arabinal... 

The conformational equilibria of methyl D-glucuronal, methyl D-galacturonal, methyl L-guluronal, and methyl L-alluronal and a number of related glycals haye been compared by means of H n.m.r. spectroscopy. An n.m.r. study of t-butyl(methyl 3 4-dideoxy-... 

Figure 6.79 Vinylogous anomeric effect, caused by (n-ir) a interactions, stabilizes axial conformers in glycals.

The conformational equilibria of the peracetylated glycals derived from four hexoses and two pentoses have been calculated by use of a molecular mechanics programme and compared with those determined by X-ray crystallography and n.m.r. spectroscopy. For the pentose derivatives there are inconsistencies between the calculated and experimental results. ... 

The addition reaction also worked with other glycals. For example, reaction with tri-O-benzyl-D-galactal 10 and benzamide afforded a 2 1 ratio of diaxiahdiequatorial addition products in 80% yield (Scheme 2). Based on the observed J values for the ring protons, it appeared as if there was no distortion from the normal conformation of the chair in this addition reaction. 

Conformational study of glycal-type neuraminidase inhibitors has been undertaken by lorga and co-workers using a combined approach of conformational analysis, molecular dynamics and quantum chemistry. /hh couplings have been calculated for the resulting conformations by the use of several already published empirical equations and compared with the experimental ones. Several examples of nucleosides and carbohydrates whose structures were obtained with the help of Vrh couplings are given in Table 2. 

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