Effects of varying the 6-position oxidation state of hexopyranoses: a systematic comparative computational analysis of 48 monosaccharide stereoisomers

Original Paper

Abstract

Knowledge of multi-dimensional carbohydrate structure is essential when delineating structure–function relationships in the development of analytical techniques such as ion mobility-mass spectrometry and of carbohydrate-based therapeutics, as well as in rationally modifying the chemical and physical properties of drugs and materials based on sugars. Although monosaccharides are conventionally presumed to adopt the canonical 4C1 chair conformation, it is not well known how altering the substituent identity around the pyranose ring affects the favored conformational state. This work provides a comprehensive and systematic computational comparison of all eight aldohexose isomers in the gas phase with reduction and oxidation at the C-6 position using density functional theory (M05-2X/cc-pVTZ(−f)//B3LYP/6-31G**) to determine the conformational and anomeric preference for each sugar in the gas phase. All 6-deoxyhexose and aldohexose isomers favored the 4C1 chair conformation, while oxidation at C-6 showed a shift in equilibrium to favor the 1C4 chair for β-alluronic acid, β-guluronic acid, and β-iduronic acid. The anomeric preference was found to be significantly affected by a remote change in oxidation state, with the alternate anomer favored for several isomers. These findings provide a fundamental platform to empirically test steric and electronic effects of pyranose substituents, with the goal of formulating straightforward rules that govern carbohydrate reactivity and drive quicker, more efficient syntheses.

Graphical abstract

A systematic comparative conformational analysis of all eight aldohexose isomers using DFT methods (M05-2X/cc-pVTZ(-f)) reveals changes in anomeric and ring conformational preference upon reduction or oxidation at the C-6 position for several sugars

Keywords

Carbohydrates Conformational analysis Density functional theory 

Notes

Acknowledgments

This material is based in part upon work supported by the National Science Foundation under CHE-1362213. A.V. acknowledges partial support for this work as a Quantitative and Chemical Biology Training Program Fellow as part of the National Institutes of Health-supported program (1 T32 GM109825-01). This research was supported in part by Lilly Endowment, Inc. through its support for the Indiana University Pervasive Technology Institute, and in part by the Indiana METACyt Initiative. The Indiana METACyt Initiative at IU is also supported in part by Lilly Endowment, Inc. We thank the Institute for Basic Science in Korea for partial support of this work (IBS-R10-D1).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

Supplementary material

894_2017_3385_MOESM1_ESM.pdf (14 mb)
ESM 1 DFT functional comparison; atomic numbering scheme; ball-and-stick structures of the lowest energy isomers; number of unique rotamers; Boltzmann distribution functional comparison (M05-2X/B3LYP/B3LYP-D3); free energies, zero point energies, entropies, and enthalpies of all rotamers; Cartesian coordinates of all rotamers (PDF 14367 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of ChemistryIndiana UniversityBloomingtonUSA
  2. 2.Department of ChemistryKorea Advanced Institute of Science and Technology (KAIST)DaejeonSouth Korea
  3. 3.Center for Catalytic Hydrocarbon FunctionalizationsInstitute for Basic Science (IBS)DaejeonSouth Korea

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