ChemInform Abstract: Conformational Studies of Oligosaccharides and Glycopeptides: Complementary of NMR, X‐Ray Crystallography, and Molecular Modelling

Wormald, Mark R.; Petrescu, Andrei J.; Pao, Ya-Lan; Glithero, Ann; Elliott, Tim; Dwek, Raymond A.

doi:10.1002/chin.200220291

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“…Compared to conventional spectroscopic methods, which are hampered by conformational averaging and offer limited structural information, computational methods are a valuable alternative that provide access to discrete conformational states and a broader understanding of the overall energetic landscape. 27 In order to fully assess the implications of deoxygenation, a large compilation of deoxysugar stereoisomers were computationally modeled in this study and a simplified scheme of these structures is provided in Figure 1. An expanded version including all discrete deoxysugar structures modeled (Figures S2 and S3), as well as a comprehensive literature compilation of all synthetic preparative routes and related computational studies (Tables S1 and S2) can be found in the SI.…”

Section: Introductionmentioning

confidence: 99%

Probing deoxysugar conformational preference: A comprehensive computational study investigating the effects of deoxygenation

Vickman

Pohl

2019

Carbohydrate Research

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Deoxysugars are intrinsic components in a number of antibiotics, antimicrobials, and therapeutic agents that often dictate receptor binding, improve efficacy, and provide a diverse toolbox in modifying glycoconjugate function due to an extensive number of unique isomers and inherent conformational flexibility. Hence, this work provides a comprehensive examination of the conformational effects associated with deoxygenation of the pyranose ring. Both the location and degree of deoxygenation were evaluated by interrogating the energetic landscape for a number of mono-and dideoxyhexopyranose derivatives using DFT methods (M05-2X/cc-pVTZ(-f)). Both anomeric forms and in some cases, the alternate chair form, have been investigated in the gas phase. As was documented in a preceding study, variation of the C-6 oxidation state has been shown to affect the anomeric preference of select glucose stereoisomers. Similar results were also observed for several deoxysugar isomers in this work, wherein the alternate anomer was favored upon reduction to the 6-deoxyhexose derivative or oxidation to the hexonic acid. Additionally, comparison of relative Gibbs free energies revealed C-3 deoxygenation imparts greater instability compared to C-2 or C-4 deoxygenation, as indicated by an increase in free energy for 3deoxysugars. A polarizable continuum solvation model was also applied to empirically validate theoretical results for several deoxysugars, wherein good agreement with both carbon (σ = 1.6 ppm) and proton (σ = 0.20 ppm) NMR shifts was observed for the majority of isomers. Solvated and gas phase anomeric ratios were also calculated and compared favorably to reported literature values, although some discrepancies are noted.

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Section: Introductionmentioning

confidence: 99%