Synthesis of Macrolide-Saccharide Hybrids by
Ring-Closing Metathesis of Precursors Derived
from Glycitols and Benzoic Acids
Marie-Christine Matos andPaul V. Murphy*
Centre for Synthesis and Chemical Biology, UCD School of
Chemistry and Chemical Biology, UCD Conway Institute,
University College Dublin, Belfield, Dublin 4, Ireland
paul.v.murphy@ucd.ie
Received October 17, 2006
Abstract:
The benzomacrolactone structural motif is a privileged or
evolutionarily selected scaffold that codes properties required
for binding to proteins and novel analogues thereof may
provide a source of new bioactive compounds. Saccharides
are also privileged structures, with (amino)sugars, iminosugars, and sugar amino acids being applied as scaffolds for
the development of nonpeptidal peptidomimetics. The syntheses of novel polyhydroxylated oxamacrolides, structural
analogues of natural polyketide derived macrolides, are
described herein, providing a basis for their development as
scaffolds. The syntheses were carried out from benzoic acids
and appropriately protected D-mannitol or D-sorbitol (D-glucitol). Ring-closing metathesis was applied in the macrocyclization step with high E-alkene selectivities being
observed. X-ray crystal structures, for two polyhydroxylated
derivatives, show that the macrocyclic rings display similar
conformations. In addition, intermolecular hydrogen-bonding
networks are observed in the lattices.
