TY - JOUR
T1 - A stepwise solvent-promoted S Ni reaction of α-d- glucopyranosyl fluoride
T2 - Mechanistic implications for retaining glycosyltransferases
AU - Chan, Jefferson
AU - Tang, Ariel
AU - Bennet, Andrew J.
PY - 2012/1/18
Y1 - 2012/1/18
N2 - The solvolysis of α-d-glucopyranosyl fluoride in hexafluoro-2- propanol gives two products, 1,1,1,3,3,3-hexafluoropropan-2-yl α-d-glucopyranoside and 1,6-anhydro-β-d-glucopyranose. The ratio of these two products is essentially unchanged for reactions that are performed between 56 and 100 °C. The activation parameters for the solvolysis reaction are as follows: ΔH ‡ = 81.4 ± 1.7 kJ mol -1, and ΔS ‡ = -90.3 ± 4.6 J mol -1 K -1. To characterize, by use of multiple kinetic isotope effect (KIE) measurements, the TS for the solvolysis reaction in hexafluoro-2-propanol, we synthesized a series of isotopically labeled α-d-glucopyranosyl fluorides. The measured KIEs for the C1 deuterium, C2 deuterium, C5 deuterium, anomeric carbon, ring oxygen, O6, and solvent deuterium are 1.185 ± 0.006, 1.080 ± 0.010, 0.987 ± 0.007, 1.008 ± 0.007, 0.997 ± 0.006, 1.003 ± 0.007, and 1.68 ± 0.07, respectively. The transition state for the solvolysis reaction was modeled computationally using the experimental KIE values as constraints. Taken together, the reported data are consistent with the retained solvolysis product being formed in an S Ni (D N ‡ A Nss) reaction with a late transition state in which cleavage of the glycosidic bond is coupled to the transfer of a proton from a solvating hexafluoro-2-propanol molecule. In comparison, the inverted product, 1,6-anhydro-β-d-glucopyranose, is formed by intramolecular capture of a solvent-equilibrated glucopyranosylium ion, which results from dissociation of the solvent-separated ion pair formed in the rate-limiting ionization reaction (D N ‡ + A N). The implications that this model reaction have for the mode of action of retaining glycosyltransferases are discussed.
AB - The solvolysis of α-d-glucopyranosyl fluoride in hexafluoro-2- propanol gives two products, 1,1,1,3,3,3-hexafluoropropan-2-yl α-d-glucopyranoside and 1,6-anhydro-β-d-glucopyranose. The ratio of these two products is essentially unchanged for reactions that are performed between 56 and 100 °C. The activation parameters for the solvolysis reaction are as follows: ΔH ‡ = 81.4 ± 1.7 kJ mol -1, and ΔS ‡ = -90.3 ± 4.6 J mol -1 K -1. To characterize, by use of multiple kinetic isotope effect (KIE) measurements, the TS for the solvolysis reaction in hexafluoro-2-propanol, we synthesized a series of isotopically labeled α-d-glucopyranosyl fluorides. The measured KIEs for the C1 deuterium, C2 deuterium, C5 deuterium, anomeric carbon, ring oxygen, O6, and solvent deuterium are 1.185 ± 0.006, 1.080 ± 0.010, 0.987 ± 0.007, 1.008 ± 0.007, 0.997 ± 0.006, 1.003 ± 0.007, and 1.68 ± 0.07, respectively. The transition state for the solvolysis reaction was modeled computationally using the experimental KIE values as constraints. Taken together, the reported data are consistent with the retained solvolysis product being formed in an S Ni (D N ‡ A Nss) reaction with a late transition state in which cleavage of the glycosidic bond is coupled to the transfer of a proton from a solvating hexafluoro-2-propanol molecule. In comparison, the inverted product, 1,6-anhydro-β-d-glucopyranose, is formed by intramolecular capture of a solvent-equilibrated glucopyranosylium ion, which results from dissociation of the solvent-separated ion pair formed in the rate-limiting ionization reaction (D N ‡ + A N). The implications that this model reaction have for the mode of action of retaining glycosyltransferases are discussed.
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U2 - 10.1021/ja209339j
DO - 10.1021/ja209339j
M3 - Article
C2 - 22148388
AN - SCOPUS:84855926382
SN - 0002-7863
VL - 134
SP - 1212
EP - 1220
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 2
ER -