Synthesis and domino metathesis of functionalized 7-oxanorbornene analogs toward cis-fused heterocycles

Ikoma, Minoru; Oikawa, Masato; Sasaki, Makoto

doi:10.1016/j.tet.2008.01.067

Cited by 33 publications

(22 citation statements)

References 57 publications

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“…The highly functionalized 7‐oxanorbornene skeleton 3 was first constructed selectively in 68 % yield by tandem Ugi/Diels–Alder reactions by using furfural and ( Z )‐3‐iodoacrylic acid for the aldehyde and carboxylic acid components, respectively (Scheme ) 4c,12. Sterically demanding iodine‐substituted acrylate was used in the intramolecular Diels–Alder reaction in a series of our study4c and also worked well in the present tandem reaction. Subsequently, four olefin groups were introduced into 3 by replacement of the iodo group.…”

Section: Resultsmentioning

confidence: 69%

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Regioselective Domino Metathesis of 7‐Oxanorbornenes and Its Application to the Synthesis of Biologically Active Glutamate Analogues

et al. 2008

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A highly regioselective domino metathesis reaction of 7-oxanorbornene was developed that employed an intramolecular association of an amide carbonyl group to a ruthenium metal centre. By using this reaction, twelve glutamate analogues inspired by dysiherbaine were efficiently synthesized over 12-14 steps; one of the analogues exhibited bioactivity consistent with central nervous system depression.

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Section: Resultsmentioning

confidence: 69%

“…Ns‐amide 4d was further converted into trifluoroacetamide (TFA‐amide) 4e in two steps (65 % yield), thereby enabling us to examine the effects of these protecting groups on the metathesis reaction. Compounds 5 and 6 ,4c which do not bear the N ‐benzyl (Bn) amide group, were also used for comparison 11…”

Section: Resultsmentioning

confidence: 99%

Regioselective Domino Metathesis of 7‐Oxanorbornenes and Its Application to the Synthesis of Biologically Active Glutamate Analogues

et al. 2008

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“…[1,20,21] Cycloaddition products of N-allyl-2-furfurylamine derivatives 1a-d ( Figure 1b)c an be subsequently manipulated with high selectivity leading to powerful synthons as well as various target molecules. [25][26][27][28][29][30][31][32][33] However,t hese derivatives do not undergo cycloaddition in an efficient manner without the use of activating or bulky protecting groups on the secondary amine,w hich aid in bringing the diene and the dienophile in close proximity in order to react. [31,34,35] Herein, we demonstrate that CB [7] promotes intramolecular [4+ +2] cycloaddition reactions,i nb iomimetic conditions,ofunactivated and unprotected N-allyl-2-furfurylamine derivatives ( Figure 1).…”

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confidence: 99%

Cucurbit[7]uril as a Supramolecular Artificial Enzyme for Diels–Alder Reactions

et al. 2017

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The ability to mimic the activity of natural enzymes using supramolecular constructs (artificial enzymes) is a vibrant scientific research field. Herein, we demonstrate that cucurbit[7]uril (CB[7]) can catalyse Diels-Alder reactions for a number of substituted and unreactive N-allyl-2-furfurylamines under biomimetic conditions, without the need for protecting groups, yielding powerful synthons in previously unreported mild conditions. CB[7] rearranges the substrate in a highly reactive conformation and shields it from the aqueous environment, thereby mimicking the mode of action of a natural Diels-Alderase. These findings can be directly applied to the phenomenon of product inhibition observed in natural Diels-Alderase enzymes, and pave the way toward the development of novel, supramolecular-based green catalysts.

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“…13 Although the reaction took place with a retention of configuration at C5, the mechanism can be reasonably understood as a sequence of elimination of hydrogen iodide followed by 1,4-conjugate addition of 9 , from a less-hindered endo face. 22 The reaction also produced a trace amount of aromatized product (structure not shown). Oxanorbornene 10 was then converted efficiently into heterotricycle 12 by domino metathesis reaction in one step, using Hoveyda–Grubbs second-generation catalyst 11 .…”

Section: Resultsmentioning

confidence: 97%

Studies on an (S)-2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid (AMPA) Receptor Antagonist IKM-159: Asymmetric Synthesis, Neuroactivity, and Structural Characterization

et al. 2013

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IKM-159 was developed and identified as a member of a new class of heterotricyclic glutamate analogues that act as AMPA receptor-selective antagonists. However, it was not known which enantiomer of IKM-159 was responsible for its pharmacological activities. Here, we report in vivo and in vitro neuronal activities of both enantiomers of IKM-159 prepared by enantioselective asymmetric synthesis. By employment of (R)-2-amino-2-(4-methoxyphenyl)ethanol as a chiral auxiliary, (2R)-IKM-159 and the (2S)-counterpart were successfully synthesized in 0.70% and 1.5% yields, respectively, over a total of 18 steps. Both behavioral and electrophysiological assays showed that the biological activity observed for the racemic mixture was reproduced only with (2R)-IKM-159, whereas the (2S)-counterpart was inactive in both assays. Racemic IKM-159 was crystallized with the ligand-binding domain of GluA2, and the structure revealed a complex containing (2R)-IKM-159 at the glutamate binding site. (2R)-IKM-159 locks the GluA2 in an open form, consistent with a pharmacological action as competitive antagonist of AMPA receptors.

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Synthesis and domino metathesis of functionalized 7-oxanorbornene analogs toward cis-fused heterocycles

Cited by 33 publications

References 57 publications

Regioselective Domino Metathesis of 7‐Oxanorbornenes and Its Application to the Synthesis of Biologically Active Glutamate Analogues

Regioselective Domino Metathesis of 7‐Oxanorbornenes and Its Application to the Synthesis of Biologically Active Glutamate Analogues

Cucurbit[7]uril as a Supramolecular Artificial Enzyme for Diels–Alder Reactions

Studies on an (S)-2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid (AMPA) Receptor Antagonist IKM-159: Asymmetric Synthesis, Neuroactivity, and Structural Characterization

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