122871-70-9Relevant articles and documents
α,ε-Hybrid foldamers with 1,2,3-Triazole rings: Order versus disorder
Milli, Lorenzo,Larocca, Michele,Tedesco, Mattia,Castellucci, Nicola,Ghibaudi, Elena,Cornia, Andrea,Calvaresi, Matteo,Zerbetto, Francesco,Tomasini, Claudia
, p. 5958 - 5969 (2014)
Two epimeric series of foldamers characterized by the presence of a repeating α,ε-dipeptide unit have been prepared and characterized by 1H NMR and ECD spectroscopies together with X-ray diffraction. The first series contains l-Ala and d-4-carboxy-5-methyl-oxazolidin-2-one (d-Oxd). The other series contains l-Ala and l-Oxd. The l,d series of oligomers forms ordered β-turn foldamers, characterized by a 311 pattern. The l,l series is not ordered. Simulations show that an ordered l,l trimer lies more than 2 kcal/mol higher than the more stable nonfolded extended conformations. Cu2+ forms complexes with both series but is not able to order the l,l series. Analysis of the EPR spectra shows that the l,d foldamers bear two types of complexation sites that are assigned as a nitrogen donor of the triazole ring and a carboxylate ligand. The l-Ala-d-Oxd-Tri-CO motif may be introduced in any peptide sequence requiring the presence of a stable β-turn conformations, like in the study of protein-protein interactions.
Synthesis and evaluation of in vivo anti-hypothermic effect of all stereoisomers of the thyrotropin-releasing hormone mimetic: Rovatirelin Hydrate
Kobayashi, Naotake,Sato, Norihito,Sugita, Katsuji,Takahashi, Kouji,Sugawara, Tamio,Tada, Yukio,Yoshikawa, Takayoshi
, (2019/11/20)
We discovered the orally active thyrotropin-releasing hormone (TRH) mimetic: (4S,5S)-5-methyl-N-{(2S)-1-[(2R)-2-methylpyrrolidin-1-yl]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl}-2-oxo-1,3-oxazolidine-4-carboxamide 1 (rovatirelin). The central nervous system (CNS) effect of rovatirelin after intravenous (iv) administration is 100-fold higher than that of TRH. As 1 has four asymmetric carbons in its molecule, there are 16 stereoisomers. We synthesized and evaluated the anti-hypothermic effect of all stereoisomers of 1, which has the (4S),(5S),(2S),(2R) configuration from the N-terminus to the C-terminus, in order to clarify the structure?activity relationship (SAR) of stereoisomers. The (4R),(5R),(2R),(2S)-isomer 16 did not show any anti-hypothermic effect. Only the (4S),(5S),(2S),(2S)-isomer 10, which has the (2S)-2-methylpyrrolidine moiety at the C-terminus showed the anti-hypothermic effect similar to 1. Stereoisomers, which have the (5R) configuration of the oxazolidinone at the N-terminus and the (2R) configuration at the middle-part, showed a much lower anti-hypothermic effect than that of 1. On the other hand, stereoisomers, which have the (4R) configuration of the oxazolidinone at the N-terminus or the (2S) configuration of the C-terminus, have little influence on the anti-hypothermic effect.
RAPID SYNTHESIS OF β-HYDROXY-α-AMINO ACIDS, SUCH AS L-THREONINE, β-HYDROXYPHENYLALANINE, AND β-HYDROXYLEUCINE, VIA AN APPLICATION OF THE SHARPLESS ASYMMETRIC EPOXIDATION
Jung, Michael E.,Jung, Young H.
, p. 6637 - 6640 (2007/10/02)
The optically active epoxy alcohols 6abc, prepared by a Sharpless kinetic resolution-epoxidation process, were converted to the optically pure β-hydroxy-α-amino acids 1abc in four steps and high overall yield.
