C-Methylated Analogs of Spermine and Spermidine: Synthesis and Biological Activity

Russian Journal of Bioorganic Chemistry - Biogenic polyamines spermine and spermidine are present in eukaryotic cells in micro- and millimolar concentrations, that determines the multiplicity of...     

Selective inhibitors of plasmepsin II of <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> on the basis of pepstatin

A number of new inhibitors of plasmepsin II (PlmII) Plasmodium falciparum, which was one of the key factors of survival of malarial parasite, was synthesized. The inhibitors were analogues of pepstatin with different substitutions for the alanine residue. Effects of the inhibitors on human PlmII and cathepsin D were studied. Inhibition of PlmII by the substrate was found. This discovery required modification of the Henderson method for determination of inhibition constants. Two synthesized inhibitors were shown to exhibit a pronounced selectivity to PlmII (K _i = 5.5 and 5 nM) in comparison with that of cathepsin D (K _i = 230 and 3000 nM, respectively).     

Convenient syntheses of phosphinic analogues of γ-aminobutyric- and glutamic acids

Three-steps, one-pot synthesis of 2-amino-4-(hydroxyphosphinyl)butyric acid from dibutyl ester of vinylphosphinic acid was carried out with an overall yield of 66%. 3-Aminopropylphosphinic acid was prepared from allylamine in three steps with an overall yield of 56%. These improved protocols allowed to obtain these commercially unavailable phosphinic analogues of glutamic acid and GABA for testing on potential molecular targets.     

The total large-scale synthesis of argiopine

The total large-scale synthesis of a natural toxin argiopine, a polymethylenepolyamine derivative, was developed. It consisted of 26 stages and included three key block schemes. Most of the stages proceeded quantitatively, which excluded the necessity of using the chromatographic separation of intermediates.