Synthesis of feralex a novel aluminum/iron chelating compound.
There is a need for in vivo applicable Fe(3+) and Al(3+) chelation compounds for use as medicines to treat toxic overload conditions of these ions. A novel compound, 2-deoxy-2-(N-carbamoylmethyl-[N'-2'-methyl-3'-hydroxypyrid-4'-one])-D-glucopyranose, designed to chelate Fe(3+) or Al(3+), has been synthesised utilising three naturally occurring products: maltol, glycine and glucosamine. The synthesis is a simple two step process. First, glycine is coupled to maltol by an aminolysis reaction, to yield the intermediate product 1-carboxymethyl -3-hdroxy-2-methylpyrid-4-one, which is joined with glucosamine using a dicyclohexylcarbodiimide promoted peptide coupling method to produce the desired end product, 2-deoxy-2-(N-carbamoylmethyl-[N'-2'-methyl-3'-hydroxypyrid-4'-one])-D-glucopyranose. The latter has been given the trivial name Feralex-G. NMR analysis permitted assignment of frequencies for all carbon and covalently bound hydrogen atoms and was consistent with the proposed structure of the compound. Electron spray Ionisation Mass Spectrometry (ESI-MS) yielded the expected molecular mass of 344. Proton displacement/pH titration analysis yielded three Feralex-G molecules bound to 1 Al(3+) or Fe(3+) over a measurable pH range of 3-10.5. A rapid TLC method to monitor progression of the synthetic procedures is also described.
Kruck
Theo P A
TP
Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S-1A1. theotheo.kruck@utoronto.ca
Burrow
Timothy E
TE
D000535:Aluminum / Q000737:chemistry*; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D017186:Titrimetry
D002614:Chelating Agents; D007502:Iron Chelating Agents; D009005:Monosaccharides; D011728:Pyridones; C447640:feralex; D000535:Aluminum; D007501:Iron