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Volumn 43, Issue 40, 2004, Pages 5386-5389

Mechanism of 4,6-O-benzylidene-directed β-mannosylation as determined by α-deuterium kinetic isotope effects

Author keywords

Carbohydrates; Glycosylation; Isotope effects; Reaction mechanisms

Indexed keywords

DEUTERIUM; PHASE TRANSITIONS; REACTION KINETICS; STEREOCHEMISTRY;

EID: 7244245511     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200453688     Document Type: Article
Times cited : (203)

References (54)
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    • In 1994 >700 glycosides were synthesized chemically using hundreds of combinations of donors and promoters: F. Barresi, O. Hindsgaul, J. Carbohydr. Chem. 1995, 14, 1043.
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    • For example see: a) B. Capon, Chem. Rev. 1969, 69, 407;
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    • (Eds.: L. C. S. Melander, W. H. Saunders), Wiley-Interscience, New York
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    • (1980) Reaction Rates of Isotopic Molecules
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    • note
    • Displacement of triflate from preformed glycosyl triflates is complete in minutes -78 °C,[11] ruling out the use of kinetic measurements, at least by the NMR methods used to characterize these intermediates.
  • 28
    • 0000939121 scopus 로고
    • On grounds of the amount of substrate needed, the substrate solubility, and the instrument time needed, direct determination of kinetic isotope effects by NMR spectroscopy at natural abundance (as in a) D. A. Singleton, A. A. Thomas, J. Am. Chem. Soc. 1995, 117, 9357;
    • (1995) J. Am. Chem. Soc. , vol.117 , pp. 9357
    • Singleton, D.A.1    Thomas, A.A.2
  • 31
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    • note
    • The critical feature is the liberation of the deuteriated mannose from 2 with neopentyl glycol and PTSA which minimizes isomerization to glucose.
  • 32
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    • note
    • 2H NMR spectroscopy was investigated but the linewidths and chemical shifts were such that the integration was compromised.
  • 34
    • 7244243856 scopus 로고    scopus 로고
    • note
    • Compound 8, a more soluble version of 1-benzenesulfinyl piperidine,[12] permits activation at -78 °C rather than the -60 °C needed for the latter.
  • 35
    • 7244227811 scopus 로고    scopus 로고
    • note
    • 2O was employed to ensure complete conversion of 6 to 9, as verified on the NMR spectrum of the crude reaction mixture following glycosylation, such that any isotope effects observed do not result from the initial activation step.
  • 37
    • 7244247095 scopus 로고    scopus 로고
    • note
    • The yield of 12 was <5%, ruling out determination of the KIE for its formation, but allowing it to be neglected in the calculation of the KIE of 11.
  • 38
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    • note
    • Ideally, comparison of the KIEs on the α- and β-products in an unselective coupling would be informative. However, this is very difficult to achieve as the method employed requires baseline resolution of the various anomeric and benzylidene acetal signals. In practice, this has proven to be a limitation with numerous substrates assayed, particularly for unselective reactions when the number of similar signals is multiplied. Second, while the reaction conditions can be manipulated[10a,b] to give predominantly the α-product it is doubtful whether measurements made under such circumstances are relevant as they presumably do not proceed via the intermediate glycosyl triflate.
  • 39
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    • note
    • D) is constant and no tunnelling occurs.
  • 44
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    • The distinction between the two mechanisms is a fine one and cannot be made on the basis of the available data. Exactly analogous problems arise in the study of the hydrolysis of simple glycosides,[25] in that of glycosyl fluorides,[26] and in enzymic glycoside hydrolysis and glycosyl transfer.[9] Comparisons with KIEs determined for enzymic reactions must, however, be treated with caution since the enzyme likely binds the substrate in a nonstandard conformation. For example: G. Sulzenbacher, H. Driguez, B. Henrissat, M. Schulein, G. J. Davies, Biochemistry 1996, 35, 15280.
    • (1996) Biochemistry , vol.35 , pp. 15280
    • Sulzenbacher, G.1    Driguez, H.2    Henrissat, B.3    Schulein, M.4    Davies, G.J.5
  • 53
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    • note
    • The fact that the covalent α-triflate 9 is so heavily favored argues against the possibility that the effects measured here result from an equilibrium isotope effect. Likewise, the highly stereoselective nature of the coupling argues against the effects measured arising from any significant shift in the equilibrium position as this would necessarily be associated with reduced selectivity.
  • 54
    • 7244248611 scopus 로고    scopus 로고
    • note
    • On the grounds that the reaction studied is highly stereoselective, and alcohol 10 is a typical carbohydrate the results obtained here may reasonably be considered as representative of this class of reactions. Of course exceptions may exist, particularly with extremely selective cases using highly reactive alcohols, but they are not likely to be representative of the formation of true interglycosidic bonds.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.