Synthesis of macrolide-saccharide hybrids by ring-closing metathesis of precursors derived from glycitols and benzoic acids.
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.
Matos
Marie-Christine
MC
Centre for Synthesis and Chemical Biology, UCD School of Chemistry and Chemical Biology, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Murphy
Paul V
PV
D001565:Benzoates / Q000737:chemistry*; D002241:Carbohydrates / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D018942:Macrolides / Q000138:chemical synthesis*; D008958:Models, Molecular; D008968:Molecular Conformation; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
D001565:Benzoates; D002241:Carbohydrates; D018942:Macrolides; D013012:Sorbitol