Synthesis and physico-chemical properties of a series of bidentate

L Saghaie, RC Hider

Abstract


Transfusion-dependent patients such as those suffering from β-thalassaemia develop a fatal secondary haemosiderosis and consequently a selective iron chelator must be used to relieve such iron overload. 3- Hydroxypyridin-4-ones are selective for iron(III) under most biological conditions, but unlike desferrioxamine, are efficiently absorbed when administered orally. In this study, the synthesis and determination of partition coefficients (Kpart) of a range of 1-substituted-2-ethyl-3-hydroxypyridin-4-ones, as orally active iron chelators, are described. All of the 1-substituted-2-ethyl-3-hydroxypyridin-4-ones were synthesized via a three step synthetic pathway. The commercially available 2-ethyl-3-hydroxypyran-4-one (ethyl maltol) was benzylated in aqueous methanol. The reaction product of the benzylated ethyl maltol with an excess of the suitable primary aryl amines was heated in a thick-walled sealed glass tube at 150-160 oC to give 1-aryl-2-ethyl-3-benzyloxypyridin-4-one derivatives which were isolated as the free-bases. Removal of the benzyl group under acidic conditions was performed by catalytic hydrogenation to yield the bidentate chelators as HCl salt in good yield. In this work, final following compounds of 1-phenyl-2-ethyl-3- hydroxypyridin-4-one, 1-(4-methylphenyl)-2-ethyl-3-hydroxypyridin-4-one, 1-(4-methoxylphenyl)-2-ethyl- 3-hydroxypyridin-4-one, and 1-(4-nitrophenyl)-2-ethyl-3-hydroxypyridin-4-one were synthesized. Identifcation and structural elucidation of ligands were achieved by 1HNMR, IR, elemental analysis, mass spectra and through physical experiments. The Kpart values of the compounds were also determined in an aqueous/octanol system using an automated continuous flow method (a filter probe method).

Keywords


Hydroxypyridinones; Partition coefficient; Iron chelator; Iron overload

Full Text:

PDF PDF PDF

Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.