Synthesis of Indole-fused 4-Pyridone-3-carboxylic Acids

Song, Ho Joon; Kim, Min Yi; Kang, Seonmi; Chung, Bong Young; Kim, Youseung

doi:10.3987/com-97-8018

Cited by 23 publications

(7 citation statements)

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“…Both underwent tin triflate-catalyzed ring closure to the pyrazinone 12 in good yield, although the cyclization of 15 proceeded more cleanly than that of its isomer 11 . These cyclizations are analogous to the methanesulfonic acid-catalyzed reactions reported previously for the des-bromo series,11a although the tin triflate procedure described here is milder and potentially more applicable to functionalized analogues. The radical-initiated cyclization of pyrazinone 12 proceeded smoothly in 90% yield to give 8 , with spectral characteristics identical to those reported for praziquantel .…”

supporting

confidence: 52%

“…Two routes to the pyrazinone intermediate 12 were investigated, by analogy to those reported by Kim et al for the des-bromo analogues 11a. These routes differ in their degree of convergence and in the direction of acetal cyclization (Scheme ).…”

mentioning

confidence: 99%

“…The ring systems differ in the positions of the carbonyl groups, although in principle they should be accessible by similar chemistry. Indeed, the syntheses that have been reported to date rely on a final Friedel−Crafts ring closure mediated by strong acid . To explore the versatility of the pyrazinone radical cyclization reaction, we applied it to a synthesis of praziquantel (Scheme ).…”

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confidence: 99%

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Amino Acid Derived Heterocycles: Lewis Acid Catalyzed and Radical Cyclizations from Peptide Acetals

2002

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Bicyclization of peptide acetals via nucleophilic attack of a phenyl group on an endocyclic acyliminium ion 4 was explored as a route to novel amino acid derived heterocycles and peptidomimetic scaffolds. In the presence of protic acid, bridged structures such as 6 are formed readily from phenylalanine derivatives, but the fused-ring analogues 5 could not be obtained in good yield. In contrast, radical cyclization of the bromophenyl dihydropyrazinone 7 provides an effective alternative for the synthesis of 5 (n = 0, 1, 2). Additional versatility in this process was demonstrated by efficient synthesis of a different fused ring system, represented by the antihelmintic praziquantel, 8.

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confidence: 99%

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confidence: 99%

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Amino Acid Derived Heterocycles: Lewis Acid Catalyzed and Radical Cyclizations from Peptide Acetals

2002

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“…There is a large body of practical synthetic chemistry involving cyclic N -acyliminium ions that contain additional heteroatoms. − A notable example is the hydantoin-based N -acyliminium ion cyclization illustrated in eq 108 . In the bromination of the 5-phenyl derivative 326 ( n = 2), the tricyclic product 327 forms spontaneously in 90% yield; there is no need for a Lewis acid such as tin(IV) chloride to generate the requisite N -acyliminium ion.…”

Section: 28 Cyclic Ions Containing Additional Heteroatomsmentioning

confidence: 99%

Cyclizations of N-Acyliminium Ions

et al. 2004

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effectively in cyclizations with N-acyliminum species. Electron-attracting substituents other than N-acyl, such as N-sulfonyl, can also be employed in analogues of N-acyliminium ion reactions. However, this review will concentrate on cyclizations of the N-acyl type, encompassing groups such as alkanoyl, aroyl, carbalkoxy, and N,N-dialkylcarbamyl, with limited coverage of sulfonyl groups. Most significantly, this review will focus on intramolecular reactions of N-acyliminium ions that result in the formation of new carbon-carbon bonds, rather than new carbonheteroatom bonds. Although β-lactam synthesis based on the cyclocondensation of imines with acid halides, Bruce E. Maryanoff earned B.S. (1969) and Ph.D. (1972) degrees from Drexel University and then conducted postdoctoral studies at Princeton University, working with Prof. Kurt Mislow. He joined McNeil Laboratories, a Johnson & Johnson subsidiary, in 1974 and advanced to Distinguished Research Fellow, the highest scientific position in the company. From 1976 to 1992, he principally worked on discovering drugs for treating central nervous system disorders; in 1992, he moved into cardiovascular research and presently leads the Vascular Research Team. Dr. Maryanoff is recognized for his work in organic and medicinal chemistry, especially the Wittig olefination reaction; peptides and peptidomimetics; antiepileptics and antidepressants; thrombin inhibitors; and protease-activated receptors. He discovered TOPAMAX topiramate, which is marketed worldwide for the treatment of epilepsy and is being developed for migraine headache. He has published 200 scientific papers, is an inventor on 60 U.S. patents, and has received two national awards, the ACS Heroes of Chemistry Award (2000) and the ACS Award in Industrial Chemistry (2003). Dr. Maryanoff is a Fellow in the American Association for the Advancement of Science and the Royal Society of Chemistry. Han-Cheng Zhang received B.S. and M.S. degrees in chemistry from Xiamen University, P.R.C., and served as a faculty member there for 5 years. He came to the United States and earned a Ph.D. degree in organic chemistry from Rensselaer Polytechnic Institute (1992), working with Prof. Doyle Daves. He joined the R. W. Johnson Pharmaceutical Research Institute as a Postdoctoral Scientist with Dr. Bruce Maryanoff and, after one year, as a Scientist. Dr. Zhang has worked as a medicinal chemist in the areas of G-protein-coupled receptors, proteases, and kinases to discover new drug candidates, recently leading a project that identified the first potent, selective antagonists for the thrombin receptor, proteaseactivated receptor 1. He is now at the level of Principal Scientist in Johnson & Johnson Pharmaceutical Research & Development. Dr. Zhang has published over 40 scientific papers and is an inventor on 13 U.S. patents (issued or pending). His scientific interests include the design and synthesis of novel therapeutic agents, heterocycles, stereoselective reactions, organometallic chemistry, and solid-phase organic synthesis. Judi...

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“…As with the acid cleavage of the amide chalcones, the side products were not seen in subsequent steps. Since α,β-unsaturated ketones will undergo conjugate addition with many nucleophiles under mild homogeneous conditions, this route should be easily extended to a variety of heterocycles derived from 1,5-dicarbonyls aside from pyridones and dihydropyridones, such as pyridines, 2-pyrones, 4-pyrans, and 1,2-diazepines . The starting chalcones are also useful building blocks since they are willing partners in conjugate additions, annulations, and Diels−Alder reactions.…”

Section: Resultsmentioning

confidence: 99%

Simple and Efficient Synthesis of 3,4-Dihydro-2-pyridones via Novel Solid-Supported Aza-Annulation

Wagman¹,

Wang²,

Nuss³

2000

J. Org. Chem.

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A diverse array of 3,4-dihydro-2-pyridones 13 were produced utilizing the unique properties of solid-supported reactions to both drive the reactions to completion and isolate the desired products. The pyridones were synthesized in high purity by a simple sequence of novel steps commencing from an acetophenone-functionalized resin. The para-substituted acetophenone 9 could be anchored to the resin through either a sulfonamide or a carboxamide linkage. The sulfonamide resin 9a, which gave the best results, was treated with several aryl aldehydes and ethoxide to give a variety of chalcones 10a-k in excellent yield (82-99%) upon TFA cleavage. Addition of either methyl or allyl malonate and DBU to 10a-k afforded smoothly the Michael adducts 11a-j (70-99%) which were subsequently cyclized in one step employing acetic acid as a catalyst and several diverse amines to give pure 3,4-dihydro-2-pyridones 13a-p in moderate to excellent yields (30-98%).

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Synthesis of Indole-fused 4-Pyridone-3-carboxylic Acids

Cited by 23 publications

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Amino Acid Derived Heterocycles: Lewis Acid Catalyzed and Radical Cyclizations from Peptide Acetals

Amino Acid Derived Heterocycles: Lewis Acid Catalyzed and Radical Cyclizations from Peptide Acetals

Cyclizations of N-Acyliminium Ions

Simple and Efficient Synthesis of 3,4-Dihydro-2-pyridones via Novel Solid-Supported Aza-Annulation

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