Ring-Closing Metathesis and Glycosylation Reactions: Synthesis and Biophysical Studies of Polyether-Linked Carbohydrate-Based Macrocyclic Nucleosides

Bis-,
tris-, and tetrakisuracil-substituted 12-, 13-, 17-, and
21-membered macrocyclic nucleoside analogues with polyether linkages,
including C2-symmetric molecules, have
been synthesized through coupling of two appropriately allylated sugar
derivatives, derived from d-glucose, followed by a sequential
ring-closing metathesis reaction using Grubbs catalysts, double-bond
reduction, and nucleoside base insertion under Vorbrüggen reaction
conditions. Spectroscopic studies on the interaction of these nucleoside
analogues with small molecules, such as the alkaloids berberine and
palmatine and the DNA intercalator ethidium bromide, revealed a change
in the absorbance and fluorescence of the small molecules suggesting
the potential use of these nucleoside molecules as a carrier of small
molecules in biological systems. Circular dichroism studies indicated
that the complexes of the nucleosides with small molecules undergo
aggregation/self-organization. This has been further evidenced by
a SEM experiment showing the binding of berberine with one of the
nucleoside derivatives, which confirms the occurrence of secondary
structure reorganization.