73903-33-0Relevant academic research and scientific papers
A concise route to (-)-kainic acid.
Nakagawa,Sugahara,Ogasawara
, p. 3181 - 3183 (2007/10/03)
A concise route to (-)-kainic acid from enantiopure (+)-cis-4-carbobenzoxyamino-2-cyclopentenol has been devised by employing concurrent Chugaev syn-elimination and intramolecular ene reaction as the key step.
Geometrical optimisation of 1,1′-binaphthalene receptors for enantioselective molecular recognition of excitatory amino acid derivatives
Lustenberger, Philipp,Martinborough, Esther,Mordasini Denti, Tiziana,Diederich, Francois
, p. 747 - 761 (2007/10/03)
A series of optically active 1,1′-binaphthalene-derived receptors with N-(pyridine-2,6-diyl)acetamide [CONH(py)] H-bonding sites in the 6,6′-positions has been prepared for the enantioselective complexation of the N-carbobenzyloxy (Cbz)-protected excitatory amino acids aspartic (Asp) and glutamic (Glu) acid via two COOH ... CONH(py) H-bonding arrays and additional secondary bonding interactions. The conformational homogeneity of the receptors is enhanced by locking the dihedral angle θ about the chirality axis through the C(1)-C(1′) bond of the 1,1′-binaphthalene moiety either by bridging the 2,2′-positions or by attaching bulky substituents to these centres. Computer modelling has shown that bridging is more efficient in locking this dihedral angle than the introduction of bulky substituents, and these predictions have been confirmed by 1H NMR binding studies in CDCl3 and in CDCl3-CD3OD 99.8:0.2. Plots of the enantioselectivity Δ(ΔG°) (difference in stability between diastereoisomeric complexes) in the recognition by the bridged receptors as a function of the enforced dihedral angle θ are peak-shaped, and the highest values have been measured in CDCl3 (300 K) for the complexation of the enantiomers of N-Cbz-Asp [Δ(ΔG°) = 6.9 kJ mol-1] and N-Cbz-Glu [Δ(ΔG°) = 5.2 kJ mol-1] by (R)-21 (θ = 86 ± 4°). The more stable diastereoisomeric complexes are highly structured, and tight host-guest bonding has been confirmed by the observation of up to five intermolecular NOEs. Enforcing the conformational homogeneity by bridging represents a new general principle for improving the chiral recognition potential of 1,1′-binaphthalene receptors.
Chiral 1,1'-binaphthyl molecular clefts for the complexation of excitatory amino-acid derivatives
Martinborough,Mordasini Denti,Castro,Wyman,Knobler,Diederich
, p. 1037 - 1066 (2007/10/02)
The complexation of N-benzyloxycarbonyl (Cbz) derivatives of the excitatory amino acids L-aspartic acid (Asp; 1), L-glutamic acid (Glu; 3), and, for the first time, L-kainic acid ((2S,3S,3S)-2-carboxy-4-(1-methylethenyl)pyrrolidine-3-acetic acid; Kai; 5) was studied in CDCl3 with a diversity of chiral receptors consisting of a 1,1'-binaphthyl spacer with (carboxamido)pyridine (CONH(py)) functionality attached to the 6,6'-positions in the major groove. Receptors of type A possess two N-(pyridin-2-yl)carboxamide H-bonding sites (e.g. 7), whereas type B-receptors have two N-(pyridine-6,2-diyl)acetamide residues attached (e.g. 8 and 9). Complexes of excitatory amino-acid derivatives and other, achiral α,ω-dicarboxylic acids with these receptors are primarily stabilized by two sets of C = O... H-N and O-H... N H-bonds. Optically active type-A receptors such as (R)- and (S)-7 showed a preference for the larger Glu derivative, whereas type-B receptors such as (R)- and (S)-8 and (R)- and (S)-9 formed more stable complexes with the smaller Cbz-Asp. To improve the poor enantioselectivity shown by 7-9, additional functionality was introduced at the 7,7'-positions of the 1,1'-binaphthyl spacer, and the nature of the H-bonding sites in the 6,6'-positions was varied. Screening the diversity of new racemic receptors for binding affinity, which had been shown in many examples by Gram to correlate with enantioselectivity, demonstrated that (±)-10 and (±)-11 formed the most stable complexes with dicarboxylic acids, and these receptors were synthesized in enantiomerically pure form. Both are type-B binders and contain additional PhCH2O (10) and MeO (11) groups in the 7,7'-positions. By 1H-NMR binding titrations, the complexation of (R)-and (S)-10 and (R)- and (S)-11 with the excitatory amino-acid derivatives was studied in CDCl3, and association constants K(a) between 103 and 2. 105 l mol-1 were measured for the 1:1 host-guest complexes formed. Whereas both 10 and 11 formed stable complexes, enantioselective binding was limited to the PhCH2O-substituted receptor 10, with the (R)-enantiomer complexing Cbz-Asp by 0.7 kcal mol-1 more tightly than the (S)-enantiomer. The structures of the diastereoisomeric complexes were analyzed in detail by experimental methods (complexation-induced changes in 1H-NMR chemical shifts, 1H{1H} nuclear Overhauser effect (NOE) difference spectroscopy) and computer modeling. These studies established that an unusual variety of interesting aromatic interactions and secondary electrostatic interactions are responsible for both the high binding affinity (-ΔG° up to 7.2 kcal mol-1) and the enantioselection observed with (R)- and (S)-10. In an approach to enhance the enantioselectivity by reducing the conformational flexibility of the 1,1'-binaphthyl spacer, an additional crown-ether binding site was attached to the 2,2'-positions in the minor groove of the type-B receptors (R)- and (S)-48. Both the binding affinity and the enantioselectivity (Δ(ΔG°) up to 0.7 kcal mol-1) in the complexation of the excitatory amino-acid derivatives by (R)- and (S)-48 were not altered upon complexation of Hg(CN)2 at the crown-ether binding site, demonstrating lack of cooperativity between the minor- and major-groove recognition sites.
Enantioselective synthesis of (-)-kainic acid
Takano,Sugihara,Satoh,Ogasawara
, p. 6467 - 6471 (2007/10/02)
Novel diastereoselectivity in the intramolecular Diels-Alder reaction of the heterodiene 18 has been observed. The structure of the cycloadduct was determined to be 20, possessing cis-5/6 ring juncture by converting it into (-)-kainic acid and kainic acid lactone.
A Concise Enantioselective Route to (-)-Kainic acid from (S)-2-(Benzyloxymethyl)oxirane
Takano, Seiichi,Iwabichi, Yoshiharu,Ogasawara, Kunio
, p. 1204 - 1206 (2007/10/02)
A concise enantioselective route to (-)-kainic acid (1) from (S)-2-(benzyloxymethyl)oxirane (2) has been established by enentio- and diastereo-selective intramolecular 1,3-dipolar cyclization.
Pelladium(II)-Catalyzed Olefin-Coupling Reactions of Kainic Acid: Effects of Substitution on the Isopropenyl Group on Receptor Binding
Convay, Gregory A.,Park, Joon Sup,Maggiora, Linda,Mertes, Mathias P.,Galton, Noemi,Michaelis, Elias K.
, p. 52 - 56 (2007/10/02)
Two palladium-catalyzed carbon-carbon bond forming reactions were found to be useful for the modification of a protected amino acid derivative containing a sterically hindered isopropenyl group.Arylation of the terminal methylene group of the dimethyl est
