Stereoelectronic effects at oxygen. A very large effect on the hydrolysis of a conformationally locked acetal: implications for β-glycosidase mechanisms

Briggs, Andrew J.; Evans, Christopher M.; Glenn, Robert; Kirby, Anthony J.

doi:10.1039/p29830001637

Cited by 29 publications

(20 citation statements)

References 8 publications

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“…This does not mean that stereoelectronic effects are not operative in these systems but simply that more constrained ring systems must be suitably designed. The rate of hydrolysis of the bicyclic phosphate 71 is 5.2 X 103 times that of the acyclic phosphate 73 while the rate of hydrolysis of the bicyclic phosphorothionate 72 is 8.1 X 102 times that of the acyclic phosphorothionate 74. 97 As can be seen from structure 75 (EtO)3P=0 °.…”

Section: Hydrolysis Of Six-membered-ring Phosphorus Heterocyclesmentioning

confidence: 95%

Stereoelectronic effects in biomolecules

Gorenstein¹

1987

Chem. Rev.

182

120

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Section: Hydrolysis Of Six-membered-ring Phosphorus Heterocyclesmentioning

confidence: 95%

Stereoelectronic effects in biomolecules

Gorenstein¹

1987

Chem. Rev.

182

120

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“…6 The extensive studies indeed generated a wealth of interesting results, but the arguments are apparently involved and -importantly -too crucially predicated on the possibility of a relatively slow nitrogen inversion. (The evidence for this is not conclusive, but the validity of ALPH is clearly supported 13 by the unreactivity of Kirby's bicyclic acetal 5.) Thus, ALPH was seriously challenged, but not finally invalidated: Deslongchamps' notional and intuitively-reasonable proposal, 2 apparently, must remain for the present!…”

Section: Methodsmentioning

confidence: 94%

“…4 ) In fact, the above condition that 3 TS and 4 TS are both equally accessible is an important one, and indicates considerable residual conformational flexibility in the corresponding model compounds 3 and 4. In the ingeniously designed bicyclic system 5, however, all relevant conformational flexibility has been obliterated: 13 in the oxocarbenium ion resulting from exocyclic C-O cleavage a lone pair on the bridging oxygen atom can only be orthogonal to the cationic p orbital at the bridgehead. Thus, ALPH predicts that 5 would be extremely unreactive, as it indeed is.…”

Section: Methodsmentioning

confidence: 99%

Some recent developments in stereoelectronic theory. Reevaluations of ALPH and the reverse anomeric effect

Chandrasekhar¹

2005

Arkivoc

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A critique of objections to the 'antiperiplanar lone pair hypothesis' (ALPH) and the 'reverse anomeric effect' (RAE) is presented. Whilst early fears that ALPH is incompatible with the Curtin-Hammett principle (CHP) were apparently unfounded, objections to ALPH based on the reactions of cyclic hemiorthoesters and amidinium salts are debatable. (The unreactivity of Kirby's bicyclic bridgehead acetal supports ALPH convincingly.) Objections to RAE were based on its apparent incompatibility with ALPH, studies on several models indicating (dubiously) the existence of a weak anomeric effect rather than RAE. However, this may well suggest that a normal anomeric effect is being offset by RAE. This apparently indicates different bases for the ground state and kinetic anomeric effects: the classical 'electrostatic gauche repulsive interaction' (EGRI) and the 'orbital interaction' (OI) respectively. The evidence against free oxocarbenium ions, but favouring the ion pair and the 'exploded transition state' (ETS) models apparently raises the question 'Whither ALPH?'. A rigorous application of the CHP to the stereochemistry of displacements at glycosyl anomeric centres, indicates that the α anomers react retentively via ion pairs, whereas the β anomers react with inversion via the ETS. (A substantial reassessment of the 'in situ anomerisation technique' is also indicated.)

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“…conformationally-locked analogues of sugars and azasugars in which the exocyclic C-O bond is very slow to cleave. 14 Vasella 15 has also reported bicyclic mimetics of saccharides 7, while Kirby and Sinaÿ 16 recently synthesised bicyclic molecule 8 which resembles closely the B 2,5 conformation, a candidate for the one adopted by the glucopyranosyl oxacarbenium ion. All these studies used carbohydrate starting materials to provide most of the functionality in the products and ensure stereocontrol.…”

Section: Introductionmentioning

confidence: 99%

Towards novel difluorinated sugar mimetics; syntheses and conformational analyses of highly-functionalised difluorinated cyclooctenones

et al. 2005

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This version is available at https://strathprints.strath.ac.uk/10080/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Highly-functionalised difluorinated cyclooctenones were synthesised from trifluoroethanol using either metallated difluoroenol acetal or carbamate chemistry, followed by a [2,3]-Wittig rearrangement or aldol reaction. Efficient RCM reactions afforded the title compounds which showed rather restricted fluxional behaviour by VT 19 F NMR. Topological characterisation by molecular modelling and NOESY/ROESY experiments offered a number of challenges, but allowed the identification of two favoured boat-chair conformers which interconverted by pseudorotation with relatively large activation barriers.

show abstract

Stereoelectronic effects at oxygen. A very large effect on the hydrolysis of a conformationally locked acetal: implications for β-glycosidase mechanisms

Cited by 29 publications

References 8 publications

Stereoelectronic effects in biomolecules

Stereoelectronic effects in biomolecules

Some recent developments in stereoelectronic theory. Reevaluations of ALPH and the reverse anomeric effect

Towards novel difluorinated sugar mimetics; syntheses and conformational analyses of highly-functionalised difluorinated cyclooctenones

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