Chapter 4 Computational Studies of the Role of Glycopyranosyl Oxacarbenium Ions in Glycobiology and Glycochemistry

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This chapter discusses the computational studies about the role of glycopyranosyl oxacarbenium ions in glycobiology and glycochemistry. An understanding of the formation and breaking of glycosidic linkages is at the core of both glycobiology and glycochemistry. With only a few exceptions, both the formation and breaking of glycosidic linkages involve processes that proceed through species having a high degree of oxacarbenium ion character. Two current reports have studied model systems for glycopyranosides— namely, 2-methoxytetrahydropyran and 2-ethoxytetrahydropyran, with special emphasis on determining precisely the anomeric effect. To achieve these goals, a so-called complete basis set (CBS) calculation was performed in the gas phase at 0 K. To reach agreement with the experiment, the standard corrections of including the zero point energy, a temperature correction to room temperature, and estimating the entropy were added. One of the many factors that affect the reactivity and stability of the glycopyranosyl oxacarbenium ion is the orientation and the conformation of the side chains attached to C-2, C-3, C-4, and C-5. In this study the implications for reactivity of the different stereochemistry, and hence orientations at C- 4 of galacto-versus gluco-configured ions are one of the main considerations. The C-5–C -6 conformation has also been extensively studied in neutral oligosaccharides.

Introduction

Unraveling the mechanistic details of the myriad of glycosyl processing enzymes (GPEs)1, 2, 3, 4 is a major endeavor of numerous scientists since these enzymes are essential to many industries, ranging from such biomass utilization industries as bioethanol and paper production through the varied fermentation processes of the food and beverage industries, to the production of aminoglycoside antibiotics and carbohydrate conjugate vaccines by the pharmaceutical industries.5 Behind all this glycobiology are the decades of developments by carbohydrate chemists to isolate, identify, and synthesize the substrates and products of many of these enzymes. Such studies are an integral part of elucidating the fundamental structure–function relationships that underlie the practical application of these compounds.6, 7, 8 Many of these processes involve the formation or breaking of glycosidic bonds. Consequently, an understanding of the formation and breaking of glycosidic linkages is at the core of both glycobiology and glycochemistry.

With only a few exceptions, both the formation and breaking of glycosidic linkages involve processes that proceed through species having a high degree of oxacarbenium ion character. Thus, in the chemistry of, glycofuranosyl and glycopyranosyl groups, as the two commonest ring forms of sugars, an understanding of oxacarbenium ions is a very important area of research. Because of the transient nature of oxacarbenium ions, their properties are very difficult to establish experimentally.9, 10 For this reason one of the strategies for establishing their structures and their conformational preferences is to perform quantum mechanical (QM) studies. QM is the computational method of choice, since the ions by definition contain a trigonal carbon atom and one must consider subtle charge‐delocalization effects, and neither factor is readily amenable to any other computational method. In the past 10 or so years computational resources and software have become available that allow for the practical study of such species.11, 12 Since a number of these studies have been conducted in the author's laboratory in Ottawa, this chapter presents a study of the d‐galactopyranosyl system, prepared specifically for this contribution. It should enable those readers having access to the appropriate software and hardware, to perform their own studies of sugars of interest. Here the results for the galactopyranosyl system are compared and contrasted with published results for other carbohydrates, and in this way pertinent examples from the literature are presented. A diligent attempt has been made to provide both recent and classical references to the fundamental principles and relevant experimental studies. No detailed understanding of computational chemistry is expected of the reader, but some familiarity with either or both of chemical glycosylation reactions and GPE‐catalyzed reactions is helpful.

Section snippets

Background

In what is generally considered a classic paper in carbohydrate chemistry, Edwards provided compelling evidence that galactopyranosides are hydrolyzed faster than their gluco counterparts.13 In a variety of other situations this higher reactivity seems to be general; galactopyranosyl donors are almost always more reactive than glucopyranosyl donors having the same protecting and leaving groups, in chemical glycosylations under similar reaction conditions.14 The simplest explanation of this

Summary of Glycosylation Reaction Mechanisms

Selected points from the vast glycosylation literature have been presented which are intended to complement the results shown for galactopyranosyl oxacarbenium ions related to 2 and 17. A number of little recognized parameters previously described for other glycopyranosyl oxacarbenium ions have been identified for 2 and 17 that help to suggest their generality. A summary is made below:

  • (1)

    The 5S1 conformation of glycopyranosyl oxacarbenium ions with O‐2 equatorial and the remaining substituents

Acknowledgments

The author acknowledges the assistance of various collaborators, visiting scientists, and postdoctoral fellows who have made this research possible. These include J. J. Krepinsky, T. Nukada, A. Bérces, M. Z. Zgierski, L.‐J. Wang, and A.R. Ionescu.

References (235)

  • T. Nukada et al.

    Can the stereochemical outcome of glycosylation reactions be controlled by the conformational preferences of the glycosyl donor?

    Carbohydr. Res.

    (2002)
  • G.I. Csonka

    Proper basis set for quantum mechanical studies of potential energy surfaces of carbohydrates

    J. Mol. Struct. (Theochem)

    (2002)
  • N. Miura et al.

    A theoretical study of α‐ and ß‐d‐glucopyranose conformations by the density functional theory

    Chem. Phys. Lett.

    (2006)
  • U. Schnupf et al.

    DFT studies of the disaccharide, α‐maltose: Relaxed isopotential maps

    Carbohydr. Res.

    (2007)
  • Y. Kurihara et al.

    An investigation of the pyranose ring interconversion path of α‐L‐idose calculated using density functional theory

    Carbohydr. Res.

    (2006)
  • H.L. Woodcock et al.

    Ab initio modeling of glycosyl torsions and anomeric effects in a model carbohydrate: 2‐ethoxy tetrahydropyran

    Biophys. J.

    (2007)
  • I. Tvaroška et al.

    The anomeric and exo‐anomeric effects of a hydroxy group and the stereochemistry of the hemiacetal linkage

    Carbohydr. Res.

    (1998)
  • M. Hricovíni

    B3LYP/6–311++G** study of structure and spin‐spin coupling constants in methyl 2‐O‐sulfo‐α‐L‐iduronate

    Carbohydr. Res.

    (2006)
  • R.U. Lemieux

    Some implications in carbohydrate chemistry of theories relating to the mechanisms of replacement reactions

    Adv. Carbohydr. Chem.

    (1954)
  • A.R. Ionescu et al.

    Investigations into the role of oxacarbenium ions in glycosylation reactions by ab initio molecular dynamics

    Carbohydr. Res.

    (2006)
  • T. Nukada et al.

    The two conformer hypothesis: 2,3,4,6‐tetra‐O‐methyl‐ mannopyranosyl‐ and ‐glucopyranosyl oxacarbenium ions

    Carbohydr. Res.

    (2005)
  • A. Bérces et al.

    Quantitative description of six‐membered ring conformations following the IUPAC conformational nomenclature

    Tetrahedron

    (2001)
  • Z. Li et al.

    An armed‐disarmed approach for blocking aglycon transfer of thioglycosides

    Tetrahedron Lett.

    (2007)
  • R. Geurtsen et al.

    Chemoselective glycosylations of sterically hindered glycosyl acceptors

    Tet. Lett.

    (2002)
  • I. Braccini et al.

    Conformational analysis of nitrilium intermediates in glycosylation reactions

    Carbohydr. Res.

    (1993)
  • V. Magnus et al.

    Competitive formation of peracetylated α‐L‐arabinopyranosides and ß‐L‐arabinose 1,2‐(alkyl orthoactetates) in Koenigs‐Knorr condensations

    Carbohydr. Res.

    (1983)
  • G.E. Whitworth et al.

    Analysis of PUGNAc and NAG‐thiazoline as transition state analogues of human O‐GlcNAcase: Mechanistic and structural insights into inhibitor selectivity and transitions state poise

    J. Am. Chem. Soc.

    (2007)
  • M.L. Sinnott

    Catalytic mechanisms of enzymatic glycosyl transfer

    Chem. Rev.

    (1990)
  • A.J. Bennet et al.

    Mechanisms of glycopyranosyl and 5‐thioglycopyranosyl transfer reactions in solution

    J. Chem. Soc. Perkin Trans II

    (2002)
  • C.‐H. Wong

    Carbohydrate‐based Drug Discovery

    (2003)
  • D.M. Whitfield et al.

    Glycosylation reactions – Present status future directions

    Glycoconjugate J.

    (1996)
  • H. Paulsen

    Advances in selective chemical syntheses of complex oligosaccharides

    Angew. Chem. Int. Ed.

    (1982)
  • N.S. Banait et al.

    Reactions of anionic nucleophiles with α‐d‐glucopyranosyl fluoride in aqueous solutions through a concerted ANDN (SN2) mechanism

    J. Am. Chem. Soc.

    (1991)
  • T.L. Amyes et al.

    Lifetimes of oxocarbenium ions in aqueous solution from common ion inhibition of the solvolysis of α‐azido ethers by added azide ion

    J. Am. Chem. Soc.

    (1989)
  • A.G. Gerbst et al.

    Computation techniques in the conformational analysis of carbohydrates

    Russ. J. Bioorg. Chem.

    (2007)
  • C.O. da Silva

    Carbohydrates and quantum chemistry: How useful is this combination?

    Theor. Chem. Acta

    (2006)
  • J.T. Edward

    Stability of glycosides to acid hydrolysis

    Chem. Ind.

    (1955)
  • F.H. Newth et al.

    The reactivity of the O‐acylglycosyl halides. Part III. Steric effects

    J. Chem. Soc.

    (1953)
  • K.N. Kirschner et al.

    Solvent interactions determine carbohydrate conformation

    Proc. Natl. Acad. Sci.

    (2001)
  • H.H. Jensen et al.

    Steric effects are not the cause of the rate difference in hydrolysis of stereoisomeric glycosides

    Org. Lett.

    (2003)
  • M. Miljković et al.

    Experimental and theoretical evidence of through‐space electrostatic stabilization of the incipient oxocarbenium ion by an axially oriented electronegative substituent during glycopyranoside acetolysis

    J. Org. Chem.

    (1997)
  • D.M. Smith et al.

    Electrostatic interactions in cations and their importance in biology and chemistry

    Org. Biomol. Chem.

    (2006)
  • C.G. Lucero et al.

    Stereoselective C‐glycosylation reactions of pyranoses: The conformational preference and reactions of mannosyl cation

    J. Org. Chem.

    (2006)
  • S.R. Shenoy et al.

    Nucleophilic additions of trimethylsilyl cyanide to cyclic oxocarbenium ions: Evidence for the loss of stereoselectivity at the limits of diffusion control

    J. Am. Chem. Soc.

    (2006)
  • J. Screen et al.

    IR‐spectral signatures of aromatic‐sugar complexes: Probing carbohydrate–protein interactions

    Angew. Chem. Int. Ed.

    (2007)
  • R.A. Jockusch et al.

    Probing the glycosidic linkage: UV and IR ion‐dip spectroscopy of a lactoside

    J. Am. Chem. Soc.

    (2004)
  • P. Çarçabal et al.

    Building up key segments of N‐glycans in the gas phase: Intrinsic structural preferences of the α(1,3) and α(1,6) dimannosides

    J. Am. Chem. Soc.

    (2006)
  • R.A. Jockusch et al.

    Sugars in the gas phase part 2: The spectroscopy of jet‐cooled phenyl ß‐d‐galactopyranoside

    Phys. Chem. Chem. Phys.

    (2003)
  • J.‐Y. Salpin et al.

    Gas‐phase acidity of d‐glucose. A density functional theory study

    J. Mass Spectrom.

    (2004)
  • Y.K. Sturdy et al.

    Torsional anharmonicity in the conformational analysis of ß‐d‐galactose

    J. Phys. Chem. B

    (2006)
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