- Production method of optically active diphenylalanine compounds
-
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
- -
-
Page/Page column 22
(2008/06/13)
-
- Synthesis of enantiomerically pure β,β-diphenylalanine (Dip) and fluorenylglycine (Flg)
-
A new strategy for the preparation of both enantiomers of two phenylalanine analogues, β,β-diphenylalanine and fluorenylglycine, has been developed. The combination of a high yielding racemic synthesis and a very efficient resolution procedure has provided significant amounts of each amino acid in enantiomerically pure form and suitably protected for use in peptide synthesis. This methodology can be easily applied to the preparation of larger quantities of enantiopure compounds.
- Royo, Soledad,Jimenez, Ana I.,Cativiela, Carlos
-
p. 2393 - 2400
(2007/10/03)
-
- Design and Synthesis of Side-Chain Conformationally Restricted Phenylalanines and Their Use for Structure-Activity Studies on Tachykinin NK-1 Receptor
-
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.
- Josien, Hubert,Lavielle, Solange,Brunissen, Alie,Saffroy, Monique,Torrens, Yvette,et al.
-
p. 1586 - 1601
(2007/10/02)
-
- Asymmetric synthesis of L-diphenylalanine and L-9-fluorenylglycine via room temperature alkylations of a sultam-derived glycine imine
-
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.
- Josien,Martin Chassaing
-
p. 6547 - 6550
(2007/10/02)
-
