Phenanthrylalkanoic Acids I: Syntheses and Biological Activities of 1‐Phenanthryl Derivatives

Eirin, A.; Fernández, Fernando Nieto; Gómez, Generosa; López, Carmen; Santos, A.; Calleja, José María; Iglesia, Dolores De La; Cano, Ernesto

doi:10.1002/ardp.198700018

Cited by 12 publications

(3 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Reformatsky reaction of phenanthrenones 6b , c with ethyl α-bromopropionate, followed by the dehydratation of the resulting β-hydroxyester in refluxing formic acid (Scheme ), proved to be the most convenient route leading to ethyl 2-(3,4-dihydrophenanthren-1-yl)propionates 10a − c . DDQ-promoted aromatization of the latter in benzene at 55 °C, followed by the hydrolysis of the resulting 2-phenanthrylpropionates 11a − c in methanolic KOH, afforded the corresponding 2-(phenanthren-1-yl)propionic acids 1a − c in approximately 70% overall yields.…”

Section: Resultsmentioning

confidence: 99%

“…Apart from the intrinsic importance of the selective functionalization of polycyclic arenes, our interest in this class of aromatics arose from the observation that phenanthrene nucleus is at the base of several enzyme inhibitors and other pharmacologically important drugs . In this connection, it was reported that 2-(phenanthr-1-yl)propionic acid ( 1a ) exhibits a biological activity as NSAID comparable to that of common registered profens such as fenbufen . In this article, we suggest a general approach to nucleus and/or side-chain regioselectively fluorinated 2-(phenanthryl)propionic acids on the basis of an original combination of radical and organometallic chemistry.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regioselectively Nucleus and/or Side-Chain Fluorinated 2-(Phenanthryl)propionic Acids by an Effective Combination of Radical and Organometallic Chemistry

Ricci

Ruzziconi

2004

J. Org. Chem.

View full text Add to dashboard Cite

Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthr-1-yl)- and 2-(phenanthr-2-yl)propionic acids 1-5 were prepared using phenanthren-1(2H)-ones 6a-c as key intermediates. Thus, ethyl 2-(fluorophenanthryl)propionates 11 were obtained in good yields by Reformatsky reaction of 6a-c with ethyl 2-bromopropionate followed by dehydratation and DDQ-promoted aromatization of the resulting beta-hydroxyesters. Side-chain alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 14 were obtained by bromine/lithium permutation of dihydrophenanthryl bromides 12a-c with butyllithium followed by quenching of the lithiated intermediates with methyl pyruvate or ethyl 3,3,3-trifluoropyruvate and subsequent DDQ-promoted aromatization. The alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 25 were prepared by reacting 8-bromo-1,3-difluorophenanthrene 24 with butyllithium for 10 seconds at -110 degrees C and subsequent addition of the suitable pyruvate to the lithiated intermediates. Alkyl 2-hydroxy-2-(phenanthr-2-yl)propionates 26 and 29 were suitably obtained by site-selective metalation of 1,3-difluorophenanthrene 28 and the bromophenanthrene 24, respectively, with LDA followed by quenching of the metalated intermediates with the suitable alkyl pyruvate. Fluorination of the above alpha-hydroxypropionates with DAST, followed by the alkaline hydrolysis, allowed the expected 2-(phenanthryl)propionic acids 1-5 to be obtained in satisfactory overall yields.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regioselectively Nucleus and/or Side-Chain Fluorinated 2-(Phenanthryl)propionic Acids by an Effective Combination of Radical and Organometallic Chemistry

Ricci

Ruzziconi

2004

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…Since the biological activity of 2-(phenanthren-1-yl)propionic acid as a NSAID was reported to be similar to that of fenbufen [8], a number of nucleus and/or side-chain fluorinated 2-phenantrylpropionic acids were prepared [9], in order to assess the effect of fluorine on the structure/activity relationship with respect to its position and to the configuration of the chiral carbon. Nevertheless, a reliable study on the relationship between stereochemistry and biological activity requires a full stereochemical characterization of the compounds under investigation.…”

Section: Introductionmentioning

confidence: 99%

Stereochemical characterization of fluorinated 2-(phenanthren-1-yl)propionic acids by enantioselective high performance liquid chromatography analysis and electronic circular dichroism detection

Bertucci

Pistolozzi

Tedesco

et al. 2012

Journal of Chromatography A

View full text Add to dashboard Cite

Phenanthrylalkanoic acids, II: Syntheses and Antiinflammatory Activity of 2‐, 3‐ and 9‐Phenanthryl‐ and 9‐Chloro‐3‐phenanthrylacetic Acids

Fernández

Gómez

López

et al. 1988

Archiv der Pharmazie

Self Cite

View full text Add to dashboard Cite

Application of Willgerodt-Kindler reaction to the phenanthryl ketones la-d led to the thiomorpholides 2a-d, hydrolysis produced the acids mentioned in the title. An alternative route, of much better yield, was based on Phenanthrylalkansauren, 11: Synthese und entzundungshemmende Wirksamkeiten von 2-, 3-und 9-Phenanthryl-und 9-Chlor-3-phenanthrylessigsiiuren the oxythallation of la-d to give the methyl arylacetates 4 -4 which were Our interest for the exploration of the antiinflammatory properties of phenanthrylalkanoic acids') led us to perform the synthesis and pertinent pharmacological tests of the 2-phenanthrylacetic (3a), 3-phenanthrylacetic (3b), 9-phenanthrylacetic (3c) and 9-chloro-3-phenanthrylacetic (3d) acids.For the preparation of these compounds the clasical Willgerodt-Kindler reaction'), was first taken into consideration (Scheme l), since the acetyl derivatives la-d needed as starting materials would be commercially available and/or can be prepared easily3! None of the crude products from the Willgerodt-Kindler reactions of la-d solidified spontaneously and generally failed to crystallize from any solvent. Once purified by column-chromatography they gave TLC homogeneous materials that had to be recrystallized several times until sharp melting samples could be got. Only the thiomorpholide 2a had been previously reported by Gore et aL4); they quoted for it a m. p. 32 "C lower than that obtained by us. Identity and purity of our product 2a was undoubtfully checked by analytical and spectroscopic means (IR, NMR, MS); the product referred to by G o r d as 2a, if pure, could only be a polymorphism of ours. The barrier of the rotation around the C-N bond in simple thioamides can be as high a s 25 KcaI/mols), giving rise even to i?/E isomerism at room temp. in certain cases6), but such a situation is prevented here by the symmetry of the morpholine ring.'H-NMR spectra of all our thioamides showed the presence of four groups of signals, each for every methylene group of the morpholine moiety, occasionally seen as four slighty distorted triplets, though often the two central ones were mixed and are given as a multiplet. Differences in chemical shifts between these signals are attributed to the fact of methylene groups being a-with regard to the N or 0 atom, and s-cis cq s-trans with regard to the arylmethyl moiety, while virtual multiplicity and coupling constants point out to the near equivalence of both protons of each methylene group, thus meaning a fast chair-chair interconversion. On the other hand, MS of both 2a and 2b were very similar, indicating that their most important fragmentation patterns are due to their common aliphatic moiety. Fragmentations giving rise to their most prominent peaks are depicted in Scheme 2.Acid hydrolysis of the thiomorpholides 2a-d led to the corresponding acids 3a-d, with low to moderate yields (alkaline hydrolysis of 2b gave a poorer yield of 3b): these yields are referred to the products isolated after a first recrystallization or a reprecipitation from an alkaline extra...

show abstract

Phenanthrylalkanoic Acids I: Syntheses and Biological Activities of 1‐Phenanthryl Derivatives

Cited by 12 publications

References 15 publications

Regioselectively Nucleus and/or Side-Chain Fluorinated 2-(Phenanthryl)propionic Acids by an Effective Combination of Radical and Organometallic Chemistry

Regioselectively Nucleus and/or Side-Chain Fluorinated 2-(Phenanthryl)propionic Acids by an Effective Combination of Radical and Organometallic Chemistry

Stereochemical characterization of fluorinated 2-(phenanthren-1-yl)propionic acids by enantioselective high performance liquid chromatography analysis and electronic circular dichroism detection

Phenanthrylalkanoic acids, II: Syntheses and Antiinflammatory Activity of 2‐, 3‐ and 9‐Phenanthryl‐ and 9‐Chloro‐3‐phenanthrylacetic Acids

Contact Info

Product

Resources

About