Intramolecular Diels−Alder Reactions of 3-(Tetrahydropyridinyl)indoles:  Stereoselective Synthesis of Novel Pentacyclic Ring Systems

Gharagozloo, Parviz; Miyauchi, Masao; Birdsall, B.; Birdsall, N. J. M.

doi:10.1021/jo971981+

Cited by 11 publications

(5 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several nitrogen-rich π-extended acenaphthylenes have been obtained, characterized by the presence of one or two N atoms at the junction of five- and six-membered rings. Such systems, which typically contain ketone or lactam functionalities, were reported by Schefczik ( C52.1 , Chart ), Kappe and co-workers ( C52.2 , C52.3 , C52.5 ), Möhrle and Seidel ( C52.4 ), Gharagozloo et al ( C52.6 ), Kovtunenko et al ( C52.7 ), and Koutentis et al ( C52.8 ) . In contrast to C52.1 – 7 , which were synthesized by classical condensation methods, compound C52.8 was obtained via Ag I -mediated Pd-catalyzed cyclizations, of either oxidative or nonoxidative character.…”

Section: Nonbenzenoid Fusionmentioning

confidence: 82%

Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications

et al. 2016

View full text Add to dashboard Cite

Two-dimensionally extended, polycyclic heteroaromatic molecules (heterocyclic nanographenes) are a highly versatile class of organic materials, applicable as functional chromophores and organic semiconductors. In this Review, we discuss the rich chemistry of large heteroaromatics, focusing on their synthesis, electronic properties, and applications in materials science. This Review summarizes the historical development and current state of the art in this rapidly expanding field of research, which has become one of the key exploration areas of modern heterocyclic chemistry.

show abstract

Section: Nonbenzenoid Fusionmentioning

confidence: 82%

Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications

et al. 2016

View full text Add to dashboard Cite

show abstract

“…We synthesized several novel ring scaffolds of type 7 (in which ring C was both saturated and unsaturated), readily accessible by an intramolecular [4 + 2]π cycloaddition procedure of 1-substituted-3-(tetrahydropyridinyl)indoles previously reported. 32 Taking into consideration the affinity and cooperativity of these ring systems and their relative ease of synthesis, the pentacyclic carbazolones 22a and 23a were chosen as templates for the development of more potent allosteric agents. In this paper we present our data on the effect of ring substitution in 22a and 23a where the aim was to increase affinity while maintaining R > 1 or at least close to unity for the antagonist NMS and for ACh.…”

Section: Design Of Novel Muscarinic Allosteric Agentsmentioning

confidence: 99%

“…This enabled both the nature and the spatial position of the amino group to be readily investigated in the anticipation that both affinity and cooperativity might be optimized. We synthesized several novel ring scaffolds of type 7 (in which ring C was both saturated and unsaturated), readily accessible by an intramolecular [4 + 2]π cycloaddition procedure of 1-substituted-3-(tetrahydropyridinyl)indoles previously reported . Taking into consideration the affinity and cooperativity of these ring systems and their relative ease of synthesis, the pentacyclic carbazolones 22a and 23a were chosen as templates for the development of more potent allosteric agents.…”

Section: Design Of Novel Muscarinic Allosteric Agentsmentioning

confidence: 99%

“…We previously described an efficient four-step synthetic route to a variety of pentacyclic carbazolones via the intramolecular [4 + 2]π cycloaddition of 3-(tetrahydropyridinyl)indoles (THPIs) . Following this procedure, we were able to prepare two series of pentacyclic carbazolones 22a − aa and 23a − i , illustrated by Schemes and and incorporating a variety of substituents.…”

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Substituted Pentacyclic Carbazolones as Novel Muscarinic Allosteric Agents: Synthesis and Structure−Affinity and Cooperativity Relationships

et al. 2002

Self Cite

View full text Add to dashboard Cite

Two series of pentacyclic carbazolones, 22 and 23, have been synthesized utilizing a facile intramolecular Dielsminus signAlder reaction and are allosteric modulators at muscarinic acetylcholine receptors. Their affinities and cooperativities with acetylcholine and the antagonist N-methylscopolamine (NMS) at M(1)minus signM(4) receptors have been analyzed and compared. All of the synthesized compounds are negatively cooperative with acetylcholine. In contrast, the majority of the compounds exhibit positive cooperativity with NMS, particularly at M(2) and M(4) receptors. The subtype selectivity, in terms of affinity, was in general M(2) > M(1) > M(4) > M(3). The largest increases in affinity produced by a single substitution of the core structure were given by the 1-OMe (22b) and 1-Cl (22d) derivatives. The position of the N in the ring did not appear to be important for binding affinity or cooperativity. Two compounds 22y and 23i, both trisubstituted analogues, were the most potent compounds synthesized, with dissociation constants of 30minus sign100 nM for the M(2) NMS-liganded and unliganded receptor, respectively. The results indicate that the allosteric site, like the primary binding site, is capable of high-affinity interactions with molecules of relatively low molecular weight.

show abstract

“…When this was performed under a stream of argon the expected adduct ( 161 ) underwent 1,4- elimination of hydrogen to give the piperidyl carbazole ( 163 ). Whereas under a static atmosphere of argon, acid catalysed shift of the alkene bond gave the thermodynamically more stable enamine, which underwent cycloaddition to give the 1,4-dihydrobenzene ( 164 ) and aromatisation by 1,4-elimination of the protonated amine to give the 3-aminopropyl carbazole ( 165 ) [ 178 , 179 ].…”

Section: Muscarinic Antagonistsmentioning

confidence: 99%

Muscarinic Receptor Agonists and Antagonists

2001

View full text Add to dashboard Cite

A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes). Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

show abstract

Intramolecular Diels−Alder Reactions of 3-(Tetrahydropyridinyl)indoles: Stereoselective Synthesis of Novel Pentacyclic Ring Systems

Cited by 11 publications

References 18 publications

Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications

Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications

Substituted Pentacyclic Carbazolones as Novel Muscarinic Allosteric Agents: Synthesis and Structure−Affinity and Cooperativity Relationships

Muscarinic Receptor Agonists and Antagonists

Contact Info

Product

Resources

About