5 research outputs found
Unprecedented Biomimetic Homodimerization of Oroidin and Clathrodin Marine Metabolites in the Presence of HMPA or Phosphonate Salt Tweezers
The first biomimetic homodimerization
of oroidin and clathrodin was effected in the presence HMPA and diphosphonate
salts, strong guanidinium and amide chelating agents. The intermolecular
associations probably interfere with the entropically and kinetically
favored intramolecular cyclizations. Use of oroidin·<sup>1</sup>/<sub>2</sub>HCl salt or clathrodin·<sup>1</sup>/<sub>2</sub>HCl was indicative in the presence of the ambident nucleophilic and
electrophilic tautomers of the 2-aminoimidazolic oroidin and clathrodin
precursors. Surprisingly, the homodimerization of oroidin led to the
nagelamide D skeleton, while the homodimerization of clathrodin gave
the benzene para-symmetrical structure <b>19</b>. The common
process was rationalized from tautomeric precursors <b>I</b> and <b>III</b>
Concise synthesis of Didebromohamacanthin A and Demethylaplysinopsine: Addition of Ethylenediamine and Guanidine Derivatives to the Pyrrole-Amino Acid Diketopiperazines in Oxidative Conditions
Oxidative
nucleophilic addition of ethylenediamine and guanidine derivatives
to pyrrole-amino acid diketopiperazines was shown to provide substituted
5,6-dihydro-2Â(1<i>H</i>)-piperazinones, quinoxalinones,
and 2-aminoimidazolones. On the basis of this methodology, a concise
approach to natural products didebromohamacanthin A and demethylaplysinopsine
has been demonstrated
Uma experiĂȘncia de tradução do conto âMarcha FĂșnebreâ de Machado de Assis para o japonĂȘs
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Reporter Ligand NMR Screening Method for 2âOxoglutarate Oxygenase Inhibitors
The human 2-oxoglutarate (2OG) dependent oxygenases belong
to a
family of structurally related enzymes that play important roles in
many biological processes. We report that competition-based NMR methods,
using 2OG as a reporter ligand, can be used for quantitative and site-specific
screening of ligand binding to 2OG oxygenases. The method was demonstrated
using hypoxia inducible factor hydroxylases and histone demethylases,
and <i>K</i><sub>D</sub> values were determined for inhibitors
that compete with 2OG at the metal center. This technique is also
useful as a screening or validation tool for inhibitor discovery,
as exemplified by work with protein-directed dynamic combinatorial
chemistry
Plant Growth Regulator Daminozide Is a Selective Inhibitor of Human KDM2/7 Histone Demethylases
The JmjC oxygenases catalyze the <i>N</i>-demethylation
of <i>N</i><sup>Δ</sup>-methyl lysine residues in
histones and are current therapeutic targets. A set of human 2-oxoglutarate
analogues were screened using
a unified assay platform for JmjC demethylases and related oxygenases.
Results led to the finding that daminozide (<i>N-</i>(dimethylamino)Âsuccinamic
acid, 160 Da), a plant growth regulator, selectively inhibits the
KDM2/7 JmjC subfamily. Kinetic and crystallographic studies reveal
that daminozide chelates the active site metal via its hydrazide carbonyl
and dimethylamino groups