Anomeric effect derivatives

Anomeric effect of monosaccharides and their derivatives insights from the new QVBMM (quantized valence bond molecular mechanisms) molecular mechanics force field 98H(48)2389. 

New synthetic methods are the lifeblood of organic chemistry. Synthetic efforts toward natural products often provide the impetus for the development of novel methodology. Reactive synthons derived from 1,3-dioxanes have proven to be valuable intermediates for both syn- and anfz-1,3-diols found in many complex natural products. Coupling reactions at the 4-position of 1,3-dioxanes exploit anomeric effects to generate syu-1,3-diols (cyanohydrin acetonides), autz-1,3-diols (4-acetoxy-1,3-dioxanes), and either syn- or azztz-1,3-diols (4-lithio-1,3-dioxanes). In the future, as biologically active polyol-containing natural products continue to be discovered, the methods described above should see much use. 

On account of the more favorable anomeric effect,12 as well as of the larger nonbonding interactions of vicinal, synclinal substituents in furanoses as compared to pyranoses, jS-D-glucofuranose,13 /3-D-glucofuranurono-6,3-lactone, and their derivatives are of higher thermodynamic stability than their respective a-D anomers. 

Consequences of the conformational anomeric effect are largely expressed in monosaccharides and their derivatives. One recognizes the conformational endo-anomeric effect for pyranosides with a polar X group at C(l) (contrasteric electronic stabilization effect Fig. 7A) and conformational exo-anomeric effect for glycosides (acetals) in which the alkyl group of the exocyclic moiety is synclinal (Fig. 7B, C). 

As conformational anomeric effects represent only a fraction (—1 to —3 kcal/mol) of the global enthalpic anomeric effect or gem-dioxy stabilizing effect (—6 to —17 kcal/mol), additional factors have to be taken into account. Depending on substitution, steric factors can affect the relative stability of acetal conformers. Dubois et al.2S have demonstrated that in furanose pyranose derivatives a bulky substituent at the furanose... 

The role of the kinetic anomeric effect was demonstrated by the difference in diastereoselectivities observed for the addition of LiP03Me2 to IV-glycosylnitrone 51 and to the deoxy analogue 52. In TFIF, the difference in diastereoselectivities corresponds to a value of 1.1 kcal/mol while in CH2CI2 it gives a value of 0.6 kcal/mol. Moreover the deoxy derivative 52 undergoes a slower reaction than its parent glycosylnitrone 51. 

Carba-sugars (pseudo-sugars) and their derivatives, chemistry of, 48, 21 - 90 Carbohydrate chemistry anomeric and exo-anomeric effects in, 47, 45-123... 

A few 2,2,5,5-tetrasubstituted 1,4-dioxane derivatives were reported OR substituents tend to adopt, because of the anomeric effect, axial positions [94AX(C)625, 94MI1]. By contrast, fra J-2,5-di-OCOOR- and 2,5-di-CH2. COOR-l,4-dioxane derivatives (R = aryl, alkyl) (84JHC1197), 2-(T-uracil)-6-CH20H-l,4-dioxane (92MI2), and 2,5-di-0H-3,6-di-CH20H-l,3-... 

The conformational equilibria of 3-hydroxytetrahydro-l,3-oxazines and their 3-acetyloxy derivatives were found to be shifted toward conformers in which the lone pair on the nitrogen displayed an equatorial orientation. The preferred conformation was stabilized by a strong anomeric effect. The H NMR spectrum of 82 indicated the presence of the major and minor conformers 82a and 82b in a ratio of ca. 4 1 in CDCI3 at 243 K <1999SAA1445,... 

Both steric repulsion and anomeric effects proved to influence the conformational equilibria of 5,6-dihydro-4//-1,3-oxazines involving half-boat structures. For the /ra t-4,6-dialkyl-substituted compound 84, the conformational equilibrium was driven by steric repulsion it appeared that a 6-alkyl group in the axial position 84a is more hindered than an axial 4-alkyl 84b. However, for the /ra t, 6-diaryl-substituted derivative 85, the major conformation in the... 

Simple calculations (MM2 and HF/6-31G ), supported by a low-temperature NMR study, reveal that 2-NMc2-l,3-dioxane and the 5,5-dimethyl derivative exist exclusively in the conformation with the dimethylamino group in axial position <2001ARK(xii)58>, and DFT calculations at the B3LYP/6-31G(d,p) level of theory show that the anomeric effect of 2-Cl in 1,3-dioxane is of stereoelectronic origin while 2-F, 2-OMe, and 2-NH2 substituents on the same molecule are not <2000MI42>. 

The conformations of three 2,2 -disubstituted-l,3-dioxane derivatives 65-67 have been elucidated by NMR spectroscopy <1998CHE141, 1999PAC385, 2001ARK(xii)7> only the conformers with the more polar substituent in an axial position have been assessed as being in agreement with the anomeric effect. 

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