868523-17-5Relevant academic research and scientific papers
Synthesis of P,N-heterocycles from ω-amino-H-phosphinates: Conformationally restricted α-amino acid analogs
Queffelec, Clemence,Ribiere, Patrice,Montchamp, Jean-Luc
supporting information; experimental part, p. 8987 - 8991 (2009/04/11)
(Chemical Equation Presented) P,N-Heterocycles (3-hydroxy-1,3- azaphospholane and 3-hydroxy-1,3-azaphosphorinane-3-oxide) are synthesized in moderate yield from readily available ω-amino-H-phosphinates and aldehydes or ketones via an intramolecular Kabachnik-Fields reaction. The products are conformationally restricted phosphinic analogs of α-amino acids. The multigram-scale syntheses of the H2N(CH2) nPO2H2 phosphinic precursors (n = 1, 2, 3) and some derivatives are also described.
Design, synthesis, and activity of analogues of phosphinothricin as inhibitors of glutamine synthetase
Berlicki, ?ukasz,Obojska, Agnieszka,Forlani, Giuseppe,Kafarski, Pawel
, p. 6340 - 6349 (2007/10/03)
A new group of potent inhibitors of glutamine synthetase was designed and synthesized. The X-ray structure of bacterial glutamine synthetase complexed with phosphinothricin was used for computer-aided structure-based design of the inhibitors, in which the methyl group of phosphinothricin was chosen as the modification site. Amino and hydroxyl moieties were introduced into the phosphinic acid portion of the lead molecule to interact with ammonium binding site in the active cleft of the enzyme. Designed compounds were synthesized in enantiomerically pure form analogous to L-glutamic acid. In vitro kinetic studies with Escherichia coli glutamine synthetase confirmed the biological activity of the designed inhibitors, which with Ki values in the micromolar range (Ki = 0.59 μM for the most potent compound 2) appear to be slightly weaker inhibitors or equipotent to phosphinothricin.
