138662-63-2Relevant articles and documents
Production method of optically active diphenylalanine compounds
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Page/Page column 22, (2008/06/13)
The present invention provides a production method including reacting a diphenylmethylene halide compound represented by the following formula (1) with a malonic acid diester compound represented by the following formula (2) in an organic solvent selected
Design and Synthesis of Side-Chain Conformationally Restricted Phenylalanines and Their Use for Structure-Activity Studies on Tachykinin NK-1 Receptor
Josien, Hubert,Lavielle, Solange,Brunissen, Alie,Saffroy, Monique,Torrens, Yvette,et al.
, p. 1586 - 1601 (2007/10/02)
Constrained analogues of phenylalanine have been conceptually designed for analyzing the binding pockets of Phe7 (S7) and Phe8 (S8), two aromatic residues important for the pharmacological properties of SP, i.e., L-tetrahydroisoquinoleic acid, L-diphenylalanine, L-9-fluorenylglycine (Flg), 2-indanylglycine, the diastreomers of L-1-indanylglycine (Ing) and L-1-benzindanylglycine (Bfi), and the Z and E isomers of dehydrophenylalanine (ΔZPhe, ΔEPhe).Binding studies were performed with appropriate ligands and tissue preparations allowing the discrimination of the three tachykinin binding sites, NK-1, NK-2, and NK-3.The potencies of these agonists were evaluated in the guinea pig ileum bioassay.According to the binding data, we can conclude that the S7 subsite is small, only the gauche(-) probe 7>SP presents a high affinity for specific NK-1 binding sites.Surprisingly, the EPhe7>SP analogue, which projects the aromatic ring toward the trans orientation, is over 40-fold more potent than the Z isomer, ZPhe7>SP.A plausible explanation of these conflictual results is that either the binding protein quenches the minor trans rotamer of 7>SP in solution or this constrained amino acid side chain rotates when inserted in the protein.In position 8, the high binding affinities of 8>SP and 8>SP suggest that the S8 subsite is large enough to accept two aromatic rings in the gauche(-) and one aromatic ring in the trans direction.Peptides bearing two conformational probes in positions 7, 8 or 9 led to postulate that S7, S8, and S9 subsites are independent from each other.The volumes available for side chains 7 and 8 can be estimated to be close to 110 and 240 Angstroem3, respectively.The large volume of the S8 subsite raises question on the localization of the SP-binding site in the NK-1 receptor.If SP were to bind in the transmembrane domains, the cleft defined by the seven transmembrane segments must rearrange during the binding process in order to bind a peptide in an α-helical structure and at least one large binding subsite in position 8.Thus, indirect topographical analysis with constrained amino acids might contribute to the analysis of the receptor/ligand dynamics.Finally, this study demonstrates that a good knowledge of the peptidic backbone structure and a combination of constrained amino acids are prerequisites to confidently attribute the preferred orientation(s) of an amino acid side chain.
Asymmetric synthesis of L-diphenylalanine and L-9-fluorenylglycine via room temperature alkylations of a sultam-derived glycine imine
Josien,Martin Chassaing
, p. 6547 - 6550 (2007/10/02)
L-diphenylalanine and L-9-fluorenylglycine were prepared from a sultam-derived glycine imine 3 via room temperature-asymmetric-alkylation/hydrolysis/mild-sultam-clivage. The L-configuration was ascertained using an X-ray analysis of the alkylation product 4b.
