Journal of the American Chemical Society
Article
respectively, at the linear regression region of the Δδ/ΔT plots
for δOH at 50 mM concentration.20,33,34 These data provide an
indication that the H-bonding may exist between glycosyl
acceptor and donor. We have also observed a linear
AUTHOR INFORMATION
■
Corresponding Author
1
Notes
dependence of δOH in H NMR spectra of 2 recorded at
The authors declare no competing financial interest.
different concentrations for equimolar acceptor−donor pairs in
CDCl3 at room temperature (see the Supporting Information).
The linear dependence obtained for both 4-picolinyl donor 1d
and 4-O-picoloyl donor 1f is very indicative of the
intermolecular hydrogen bonding, as previously shown by
Vasella33,35 and Crich20 for substituted 2-aminosugars.
Last, we found that the stereoselectivity diminishes
dramatically in case of glycosyl donors protected with 4,6-O-
benzylidene (see the Supporting Information). It is possible
that the induced rigidity of the pyranose ring prevents
conformational changes necessary to form the all-axial
oxacarbenium intermediate.5,36−38 This result indicates that
the conformational flexibility of the pyranose ring might be
essential to ensure efficient H-bond-mediated aglycone delivery.
ACKNOWLEDGMENTS
■
This work was supported by an award from the NSF (CHE-
1058112). We thank Dr. Rensheng Luo (UM − St. Louis) for
aquiring spectral data using 600 MHz NMR spectrometer that
was purchased thanks to the NSF (award CHE-0959360). Dr.
Winter and Mr. Kramer (UM − St. Louis) are thanked for
HRMS determinations.
REFERENCES
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(1) Zhu, X.; Schmidt, R. R. Angew. Chem., Int. Ed. 2009, 48, 1900−
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(2) Handbook of Chemical Glycosylation: Advances in Stereoselectivity
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Weinheim, Germany, 2008.
CONCLUSIONS
■
We discovered that remote O-picolinyl and O-picoloyl groups
can mediate glycosylation reactions by providing high or even
complete facial selectivity for the attack of the glycosyl acceptor.
In our opinion, the set of data presented herein provides a
strong evidence for the hydrogen bonding between glycosyl
donor and acceptor39−42 while providing a practical new
methodology for stereoselective glycosylation. The applicability
of this approach was demonstrated and found to be consistently
effective for the synthesis of various glycosides including α- and
β-glucosides, β-galactosides, β-mannosides, and β-rhamnosides
and works well with both primary and secondary glycosyl
acceptors. Further application of this new stereoselective
glycosylation reaction to other targets and to the synthesis of
oligosaccharides along with further investigation of the
mechanism and the kinetic profile of this reaction are currently
underway in our laboratory.
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EXPERIMENTAL SECTION
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General Procedure for Glycosylation in the Presence of
DMTST. A mixture of a glycosyl donor (0.13 mmol), glycosyl acceptor
(0.10 mmol), and freshly activated molecular sieves (4 Å, 200 mg) in
(ClCH2)2 (2.6 mL, 50 mM or 26 mL, 5 mM) was stirred under argon
for 1 h. The mixture was cooled to −30 °C, DMTST18 (0.26 mmol)
was added, and the resulting mixture was allowed to warm to room
temperature over a period of 1 h. The external heating was then
applied, and the reaction mixture was stirred at 42 °C for the time
specified in tables. Alternative procedure involved stirring at room
temperature or as indicated in tables. Upon completion, Et3N (0.3
mL) was added, and the resulting mixture was stirred for 30 min. The
mixture was then diluted with CH2Cl2 (10 mL, 50 mM reaction only),
the solid was filtered off, and the residue was washed sucessively with
CH2Cl2. The combined filtrate (∼30−40 mL) was washed with 20%
aqueous NaHCO3 (10 mL) and water (3 × 10 mL). The organic
phase was separated, dried with magnesium sulfate, and concentrated
in vacuo. The residue was purified by column chromatography on
silica gel (ethyl acetate−hexane gradient elution). Anomeric ratios (or
anomeric purity) were determined by comparison of the integral
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Laptinskaya, T. V.; Kononova, E. G.; Kolotyrkina, N. G. Eur. J. Org.
Chem. 2012, 1926−1934.
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2005, 46, 5143−5147.
1
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ASSOCIATED CONTENT
* Supporting Information
Additional experimental details and characterization data for all
new compounds. This material is available free of charge via the
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dx.doi.org/10.1021/ja307355n | J. Am. Chem. Soc. 2012, 134, 20097−20102