Synthesis of an Optically Active Decahydro‐6‐isoquinolone Scaffold with a Quaternary Stereocenter

Christoffers, Jens; Scharl, Heiko; Frey, Wolfgang; Baro, Angelika

doi:10.1002/ejoc.200400055

Cited by 9 publications

(4 citation statements)

References 28 publications

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“…Finally, catalytic hydrogenation proceeded smoothly and should be performed in isopropanol as solvent in order to prevent acetal formation (if EtOH or MeOH are used). 15 The racemic products 7a and 7b now have an additional stereocenter, but they are obtained as single diastereoisomers as evidenced by NMR. Attempts to elucidate the relative configuration by ROESY experiments were not successful, but the relative configuration was established at a later stage by X-ray crystallography (vide infra) to be cis (methyl and lactam-carbonyl group).…”

Section: Resultsmentioning

confidence: 97%

Synthesis of spirocyclic carbazole- and acridine-lactams

Würdemann

Christoffers

2010

Org. Biomol. Chem.

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Spirocyclic carbazole- and acridine-lactams were prepared by Fischer-indole or Friedländer-quinoline synthesis starting from spirocyclic ketones with a lactam ring. All annulation products were obtained as mixtures of separable regioisomers, which differ only in the position of one methyl group. The starting materials were prepared from 2-pyrrolidone and 2-piperidone by a sequence of protection (by N-allylation), alpha-acylation, iron-catalyzed Michael reaction followed by Robinson-annulation, palladium-catalyzed N-deprotection and catalytic hydrogenation. The overall yields of this six-step sequence are 13 and 17%, respectively, and the racemic ketones are obtained as single diastereoisomers.

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Section: Resultsmentioning

confidence: 97%

Synthesis of spirocyclic carbazole- and acridine-lactams

Würdemann

Christoffers

2010

Org. Biomol. Chem.

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“…MPMS was synthesized using a method similar to those described in Christoffers et al (2004). MPMS-I (0.5 g, 2.3 mmol) was dissolved in EtOH (10 mL) in a Schlenk tube, degassed and placed under an argon atmosphere.…”

Section: Methodsmentioning

confidence: 99%

Cytotoxicity of thiazolidinedione-, oxazolidinedione- and pyrrolidinedione-ring containing compounds in HepG2 cells

Keil

Frederick

Jacinto

et al. 2015

Toxicology in Vitro

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Liver damage occurred in some patients who took troglitazone (TGZ) for type II diabetes. The 2,4-thiazolidinedione (TZD) ring in TGZ's structure has been implicated in its hepatotoxicity. To further examine the potential role of a TZD ring in toxicity we used HepG2 cells to evaluate two series of compounds containing different cyclic imides. N-phenyl analogues comprised 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT); 3-(3,5-dichlorophenyl)-2,4-oxazolidinedione (DCPO) and N-(3,5-dichlorophenyl)succinimide (NDPS). Benzylic compounds, which closely resemble TGZ, included 5-(3,5-dichlorophenylmethyl)-2,4-thiazolidinedione (DCPMT); 5-(4-methoxyphenylmethyl)-2,4-thiazolidinedione (MPMT); 5-(4-methoxyphenylmethylene)-2,4-thiazolidinedione (MPMT-I); 5-(4-methoxyphenylmethyl)-2,4-oxazolidinedione (MPMO); 3-(4-methoxyphenylmethyl)succinimide (MPMS) and 3-(4-methoxyphenylmethylene)succinimide (MPMS-I). Cytotoxicity was assessed using the MTS assay after incubating the compounds (0-250 μM) with HepG2 cells for 24 h. Only certain TZD derivatives (TGZ, DCPT, DCPMT and MPMT-I) markedly decreased cell viability, whereas MPMT had low toxicity. In contrast, analogues without a TZD ring (DCPO, NDPS, MPMO, MPMS and MPMS-I) were not cytotoxic. These findings suggest that a TZD ring may be an important determinant of toxicity, although different structural features, chemical stability, cellular uptake or metabolism, etc., may also be involved. A simple clustering approach, using chemical fingerprints, assigns each compound to one of three classes (each containing one active compound and close homologues), and provides a framework for rationalizing the activity in terms of structure.

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“…Use of 2-propanol instead of ethanol as the solvent prevents ketal formation at the carbonyl group. [16] Finally, we showed that the N-Boc protective group installed in compound 1f can be readily removed by a standard protocol [17] and in good yield (77 %) (Scheme 5, Table 4). …”

Section: N-deprotectionmentioning

confidence: 98%

Synthesis of 3‐Phenyl‐4‐piperidones from Acetophenone by Shapiro and Aza‐Michael Reactions and Their Further Derivatization

2007

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The Shapiro reaction of acetophenone is the key in a convenient three‐step access to a divinyl ketone which is further transformed by double aza‐Michael reactions with primary amines into N‐substituted 3‐phenyl‐4‐piperidones. In the case of N‐benzyl and N‐allyl derivatives, the piperidine nitrogen atom can be deprotected and further functionalized, for example, by carboxamide, carbamate, or urea formation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Synthesis of an Optically Active Decahydro‐6‐isoquinolone Scaffold with a Quaternary Stereocenter

Cited by 9 publications

References 28 publications

Synthesis of spirocyclic carbazole- and acridine-lactams

Synthesis of spirocyclic carbazole- and acridine-lactams

Cytotoxicity of thiazolidinedione-, oxazolidinedione- and pyrrolidinedione-ring containing compounds in HepG2 cells

Synthesis of 3‐Phenyl‐4‐piperidones from Acetophenone by Shapiro and Aza‐Michael Reactions and Their Further Derivatization

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