1
Fig. 3 Panel A: partial contour plot of the ROESY spectrum of 5 in D2O. Panel B: H NMR spectrum of compound 5; H-60 and H-600 are
indicated.
position resulted in a sensible shift of the proton resonances in
positions 1 and 6 toward lower fields; the specific downfield-shift
of H-6 from 3.77 to 4.14 ppm confirms the formation of a
phosphodiester bond in the O-6 position (Fig. 3, Panel B).7
For all the other products similar spectral features were
observed thus confirming the regioselective substitution in O-6. For
products 8–9 the NMR spectra, due to the polydisperse nature of
the starting products, did not allow the unambiguous complete
assignment of the glucopyranosidic resonances. However, for
product 8 no remarkable chemical shift differences for isopropyl
protons were found when compared to the unmodified HPCD.
Given the specific chemistry used and the MALDI-TOF results we
can reasonably conclude that the substitution in O-6 occurs.
In conclusion, we described the first regio-selective solid
phase synthesis of CDs tethered to a variety of labels through
a stable phosphodiester linkage on the C-6 position. To
demonstrate the feasibility and versatility of our synthetic
approach, monofunctionalised CDs were synthesized by using
the standard phosphotriester chemistry. MALDI-TOF MS and
NMR confirmed the selective C6-monofunctionalization of CDs.
The developed methodology can be extended to all the cyclodextrin
molecules bearing free primary OH groups and to suitable labels
that can be easily converted into phosphoramidite derivatives.
Moreover, the inclusion properties of the modified CDs can be
properly modulated by designing suitable linkers and labels.
Further studies are currently in progress to investigate
conformational properties and host–guest behaviour of some
of the synthesized compounds.
Ricerche sull’Ambiente e la Salute umana). We also thank
C.I.M.C.F., Universita degli Studi di Napoli ‘‘Federico II’’,
for the NMR and MS facilities.
Notes and references
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This study was supported by M.I.U.R. (PRIN) and
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c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 3875–3877 3877