Regioselective protection of hydantoins – essential for hydantoin based anti-epileptic drugs

The synthesis and NMR elucidation of six novel mono- and bis-Boc protected hydantoins are reported. The hydantoins 5-methylhydantoin, 5,5-dimethylhydantoin and a pentacycloundecane hydantoin exhibit an increase in substitution and steric hindrance at C-5. Kinetic and reagent controlled monoprotection of the smaller hydantoins achieve regioselective protection at N-1 while the bulky cage hydantoin is protected at N-3′. Hydantoin based anti-epileptic drugs such as 5,5-diphenylhydantoin require regioselective substitution at N-3′ for enhanced pharmaceutical activity. The study enhances our understanding of the activity of the nitrogen atoms on hydantoin rings.     

NMR and quantum chemical studies on association of 2,6-bis(acylamino)pyridines with selected imides and 2,2′-dipyridylamine

Abstract  

Association constants of 2,6-bis(alkylcarbonylamino)pyridines (alkyl = methyl or ethyl) and their perfluoroalkyl analogues with succin- and maleimide as well as with 2,2′-dipyridylamine (complementary DAD and ADA hydrogen bonding motifs are responsible for formation of the associates) have been determined by NMR titrations and quantum chemical calculations. Interactions of 2,6-bis(alkylcarbonylamino)pyridines with imides differ by character from these of perfluoroalkyl analogues. Such large difference was not observed for the 2,2′-dipyridylamine associates. Since fluorine atoms cause carbonylamino groups to be stronger hydrogen bond donors, perfluorinated species of this type were found to be more stable. Single crystal X-ray structures of 2,6-bis(trifluoromethylcarbonylamino)pyridine and 2,6-bis(pentafluoroethylcarbonylamino)pyridine have been also determined.     

Reactions of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 1,4-naphthoquinone derivatives and the properties of the obtained products

N′-(4-Oxo-1,4-dihydronaphthalen-1-ylidene)-1-phenyl-5-oxopyrrolidine-3-carbohydrazides and N′-(3-methyl-4-oxo-1,4-dihydronaphthalen-1-ylidene)-1-phenyl-5-oxopyrrolidine-3-carbohydrazides were synthesized by reactions of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 1,4-naphthoquinone or 2-methyl-1,4-naphthoquinone. The alkylated analogues of the above products were obtained using ethyl iodide. The interaction of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 2,3-dichloro-1,4-naphthoquinone was followed by formation of N′-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-1-phenyl-5-oxopyrrolidine-3-carbohydrazides. All these compounds were characterized using ¹H, ¹³C NMR, IR and mass spectra. Some of the new compounds were tested for the antimicrobial and antifungal activity.     

NMR elucidation of novel SQ109 derivatives

The NMR elucidation of five novel SQ109 analogues including SQ109 is reported herein. These derivatives were synthesized as potential anti-tuberculosis candidates. One-dimensional NMR (¹H and ¹³C) techniques show a series of overlapping signals from the methine and methylene groups of these compounds, thereby making it extremely difficult to assign all NMR signals. Two-dimensional (2D) NMR techniques were instrumental in overcoming these challenges. This paper appears to be a rare report on the complete structure elucidation of mono-substituted adamantane moieties.     

On the Reaction between 1-Aza-1,3-dienes and Push-Pull Olefins of the Acyloxymethylidene-malononitrile Type

 The reaction between push-pull olefins of the acyloxymethylidene-malononitrile type and α, β-unsaturated hydrazones affords selectively 5-alkyl-2-cyano-6-(N′,N′-dimethylhydrazono)-hexa-2,4-dienenitriles. No [4+2]-cycloaddition products were detected. The structure elucidation of the obtained compounds and possible reaction mechanisms are discussed.     

On the Reaction between 1-Aza-1,3-dienes and Push-Pull Olefins of the Acyloxymethylidene-malononitrile Type

Summary.  The reaction between push-pull olefins of the acyloxymethylidene-malononitrile type and α, β-unsaturated hydrazones affords selectively 5-alkyl-2-cyano-6-(N′,N′-dimethylhydrazono)-hexa-2,4-dienenitriles. No [4+2]-cycloaddition products were detected. The structure elucidation of the obtained compounds and possible reaction mechanisms are discussed. Received March 9, 2000. Accepted March 20, 2000     

4-Hydroxy-2-quinolones 137. Synthesis,structure, and spectroscopic characteristics of diethyl 2,2′-dioxo-1,2,3,4,1′,2′,3′,4′-octahydro[4,4′]biquinolinyl-3,3′-dicarboxylate

Treatment of the ethyl esters of 1-R-4-chloro-2-oxo-1,2-dihydroquinoline-3-carboxylic acids with zinc dust in glacial acetic acid gives high yields of diethyl 2,2′-dioxo-1,2,3,4,1′,2′,3′,4′-octahydro[4,4′]biquinolinyl-3,3′-dicarboxylates. The structural features of the synthesized compounds together with their NMR and mass spectra are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1799–1807, December, 2007.     

Intramolecular N to N acyl migration in conformationally mobile 1′-acyl-1-benzyl-3′,4′-dihydro-1′<Emphasis Type="Italic">H</Emphasis>-spiro[piperidine-4,2′-quinoline] systems promoted by debenzylation conditions (HCOONH<Subscript>4</Subscript>/Pd/C)

We report an efficient and useful synthesis of new attractive spiropiperdine scaffolds 4 based on an intramolecular acyl transfer process in 1′-acyl-1-benzyl-3′,4′-dihydro-1′H-spiro[piperidine-4,2′-quinolines] 3 using simple and mild debenzylation reaction conditions (HCOONH₄/Pd/C). The compounds 3 were prepared by acylating 1-benzyl-4′-methyl-3′,4′-dihydro-1′H-spiro[piperidine-4,2′-quinolines] 2 that are easily available from 1-benzyl-4-piperidone 1. The intramolecular character of this process was proven primarily through a crossover experiment technique. Through an examination of all spectroscopic information (¹H, ¹³C NMR, VT-¹H NMR, and ²D NMR) it was possible to correctly predict amide configurations and piperidine ring conformations of starting and final spiropiperidine compounds.      

Assignment of E/Z isomers in Schiff bases of 3-acyltetramic acids with ethylenediamine by 1H and 13C NMR spectroscopy

The reaction of ethylenediamine with an equivalent mixture of diversely substituted 3-acyltetramic acids leads to Z/Z, Z/E, E/Z and E/E isomers. The E/Z isomerisation is slow in the NMR time scale of the ¹H and ¹³C chemical shifts; therefore at room temperature and in deuterochloroform all isomers of the new synthesized asymmetric compounds N,N′-ethylene-(1-ethyl-5,5-dimethyl-1′,5′,5′-trimethyl-3,3′-acetyltetramic acid) a, N,N′-ethylene-(5,5-dimethyl-1′,5′,5′-trimethyl-3,3′-acetyltetramic acid) b and, N,N′-ethylene-(1,5,5-trimethyl-1′,5′,5′-trimethyl-3-acetyl-3′-formyl-tetramic acid) c could be found in the corresponding spectra. To assign the ¹³C NMR signals we used two-dimensional ¹³C-¹H one-bond (HMQC) and ¹³C-¹H multibond (HMBC) correlated spectroscopy and the empirical rule that CO signals involved in hydrogen bonds are shifted to a lower field. The relative stability of isomers depending on substitution pattern could be estimated from the composition of the equilibria. b crystallizes as Z/Z isomer from ethanolic solution. The X-ray structural analysis of b has shown two CH-O hydrogen bonds. Received: 31 May 1996 / Revised: 26 June 1996 / Accepted: 1 July 1996     

Thermal oxidative destruction of isomeric dipyrrolylmethanes

3,3′,4,4′-tetramethyl-5,5′-dicarboethoxydipyrrolylmethane-2,2′ and its α,β and β,β′ isomers were synthesized. The compounds were characterized by recording of their proton NMR spectra. The thermal oxidative destruction of the compounds was studied by thermogravimetry. The thermal stability of dipyrrolylmethanes was found to be primarily characterised by molecular isomerism for symmetrically substituted α,α′-and β,β′-dipyrrolylmethanes compared with α,β isomer.     

A novel chromone-substituted trimeric dihydroflavonol from <Emphasis Type="Italic">Anogeissus pendula</Emphasis>

A new chromone-substituted dihydrotriflavonol, (2S,3S)[6-{(3S) 3″,5″-dihydroxy-6″-methoxydihydrochromone}5,3′,4′,5′-tetrahydroxy-7-methoxy-3-O-8-dihydroflavone]₂ 3-O-8[6-{(3S) 3″,5″-dihydroxy-6″methoxydihydrochromone}3,5,3′,4′,5′-pentahydroxy-7-methoxydihydroflavonol] was isolated from the leaves of Anogeissus pendula. The structure was determined by UV, ¹H NMR, ¹³C NMR, HMBC, and CD data.     

Synthesis, structures, and properties of spiro[6-azaperimidine-2,4′-cyclohexa-2′,5′-dien]-1′-one derivatives

The reaction of 5-amino-4-chloroquinolines with 4-amino-2,6-di-tert-butylphenol yielded derivatives of spiro[6-azaperimidine-2,4′-cyclohexa-2′,5′-dien]-1′-one, which exhibit photo-and thermochromic properties in solutions. The structure of 2′,6′-di-tert-butyl-5,7,9-trimethylspiro[6-aza,-2,3-dihydroperimidine-2,4′-cyclohexa-2′,5′-dien]-1′-one was established by X-ray diffraction study. The ring-chain isomerization of 2′,6′-di-tert-butyl-5,7-dimethyl-and 2′,6′-di-tert-butyl-5,7,8-trimethylspiro[6-aza-2,3-dihydroperimidine-2,4′-cyclohexa-2′,5′-dien]-1′-ones was studied by dynamic NMR spectroscopy. Deceased. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2028–2034, November, 1997.     

Elucidating ‘undecipherable’ chemical structures using computer‐assisted structure elucidation approaches

Structure elucidation using 2D NMR data and application of traditional methods of structure elucidation are known to fail for certain problems. In this work, it is shown that computer‐assisted structure elucidation methods are capable of solving such problems. We conclude that it is now impossible to evaluate the capabilities of novel NMR experimental techniques in isolation from expert systems developed for processing fuzzy, incomplete and contradictory information obtained from 2D NMR spectra. Copyright © 2012 John Wiley & Sons, Ltd.     

Phytochemical analysis of young fustic (Cotinus coggygria heartwood) and identification of isolated colourants in historical textiles

Young fustic (Cotinus coggygria Scop.; Anacardiaceae) has been used as a dyestuff since antiquity. Phytochemical investigation of the methanol extract of the heartwood has led to the isolation and structure elucidation by nuclear magnetic resonance and mass spectrometry (MS) of 3′,4′,6-trihydroxyaurone (sulfuretin) and 3′,4′,7-trihydroxyflavonol (fisetin) as well as 3′,4′,7-trihydroxyflavanol (fustin), 3′,4′,5,7-tetrahydroxyflavonol (quercetin), 3′,4′,5,7-tetrahydroxyflavanol (taxifolin), 4′,7-dihydroxyflavanol, 3′,4′,7-trihydroxyflavanone (butin), 4′,7-dihydroxyflavanone (liquiritigenin), trans-2′,3,4,4′-tetrahydroxychalcone (butein), 4′,5,7-trihydroxyflavanone and trans-2′,4,4′-trihydroxychalcone (isoliquiritigenin). The isolated compounds were used as reference materials for the development of a high-performance liquid chromatography–diode array detector–MS method, which was then applied to analyse (1) fresh silk samples dyed with young fustic, (2) dyed silk subjected to artificially accelerated light ageing and (3) historical silk micro-samples, extracted from ecclesiastical post-Byzantine garments (fifteenth to eighteenth century), which belong to monasteries of Mount Athos. Sulfuretin and fisetin, which are usually used as markers for the identification of the yellow dye and, for the first time, some of the aforementioned flavonoid components of young fustic were identified in the historical extracts. Furthermore, preliminary experiments suggested that although the amounts of the dye components decrease with light ageing, the relative ratio of fisetin and sulfuretin, after a first step of ageing, seems to be almost unaffected by such degradation processes raised by light. The effect of the latter on the morphology of the dyed silk fibres is briefly investigated by scanning electron microscopy.     

Synthetic and modified isoflavonoids. XII. Synthesis of homologs of 5,7-dihydroxy-3′,4′-methylenedioxyisoflavone

Benzodioxane and benzodioxepane analogues of 5,7-dihydroxy-3′,4′-methylenedioxyisoflavone have been synthesized from α-hetaryl-2,4,6-trihydroxyacetophenones. The structures of the compounds obtained have been shown by their PMR spectra. Taras Shevchenko Kiev University. KIEN, Karakalpak Division of the Academy of Sciences of the Republic of Uzbekistan, Nukus. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 343–347, May–June, 1994.     

Anion-dependent binding of zinc calix[4]pyrrole-bisporphyrinate triethylenediamine

The complexation properties of zinc 10,20-bis[5-(2,3,7,8,12,13,17,18-octaethylporphyrinate)ethynylphenyl]-5,5′,10′,15,15′,20′-hexamethylcalix[4]pyrrole toward halide ions, triethylenediamine, and 4,4′-bipyridyl were studied by spectrophotometric titration and ¹H NMR spectroscopy. The influence of binding of anions (F⁻ and Cl⁻) by the calix[4]pyrrole fragment of zinc calixpyrrole-bisporphyrinate on the complexation properties of its interporphyrin cavity toward the bidentate organic ligand triethylenediamine.     

Another two novel ceramides from <Emphasis Type="Italic">Zephyranthes candida</Emphasis>

From the the bulbs of Zephyranthes candida (Amaryllidaceae), another two novel ceramides have been isolated and identified. The structures of the two novel compounds were established as (2S,3S,4R,21E,2′R)2-[N-(2′-hydroxynonadecanoyl)-N-(1′′,2′′-dihydroxyethyl)amino]-21-hexacosene-1,3,4-triol, named zephyranamide C (1), and 1,3,4,5,6-pentahydroxy-2-(2′-hydroxyhexacosanoyl-amino)-18-(E)-tetracosene, named zephyranamide D (2). Their structures and stereochemistries were elucidated by spectral techniques including ¹H NMR, ¹³C NMR, as well as HSQC, HMBC, DEPT, and COSY.     

Thermal behaviour and electro-optical properties of a series of liquid crystals based on palladium complexes with mixed ligands

A series of ortho-metallated palladium(II) complexes with two dimeric liquid crystals Schiff base (methoxy and decyloxy as terminal groups) as cyclometallated ligands and N-aryl-N′-benzoyl thiourea derivatives as co-ligands were prepared and investigated for their liquid crystalline properties. Their structures were assigned based on elemental analysis, FT-IR and ¹H NMR spectroscopy while the thermal behaviour was investigated by differential scanning calorimetry and polarising optical microscopy. The complexes with Schiff base ligand bearing methoxy group as terminal group show extensive decomposition during melting while the complexes with Schiff base having decyloxy group as terminal group show monotropic nematic phases, with the mesophase stability strongly related to the type of N-aryl-N′-benzoyl thiourea derivative used. Their liquid crystalline properties are compared with their analogues having N,N-dialkyl-N′-benzoyl thiourea as co-ligands which were reported previously. One of the latter complexes was also investigated by thermally stimulated depolarisation currents method while the optical transmission was recorded simultaneously. The thermally stimulated depolarisation currents and optical transmission spectra confirmed the previous observation regarding the phase transition temperatures. The current intensity–applied voltage dependencies of this complex were investigated by specific electrical measurements.     

A new biphenyl derivative from an unidentified marine fungus E33

A new biphenyl derivative 3,5′-dihydroxy-4′,5-dimethoxy-2′-methyl-[1,1′-biphenyl]-2-carboxylic acid methyl ester (1), was isolated from the culture broth of a fungus isolated from the rhizosphere soil of mangrove root on the South China Sea. The structure of 1 was determined by comprehensive spectroscopic methods, primarily 2D NMR techniques. Published in Khimiya Prirodnykh Soedinenii, No. 2, pp. 128–129, March–April, 2008.     

New sterically hindered di-o-quinones of the biphenyl series

New di-o-quinones of the biphenyl series, namely, 2,2′-dialkyl-5,5′-di-tert-butylbiphenyl-3,4,3′,4′-diquinones, were synthesized. Their structures were established by IR and NMR spectroscopy. The molecular structure of 2,2′-dimethyl-5,5′-di-tert-butylbiphenyl-3,4,3′,4′-diquinone was established by X-ray structural analysis. The structure is characterized by orthogonal (the torsion angle is 82.9°) mutual arrangement ofo-benzoquinone fragments. ESR studies demonstrated that chemical reduction of diquinone proceeds in four oneelectron stages to form paramagnetic mono- and trianions as intermediates. Quinopyrocatechols, which are intermediates in the synthesis of di-o-quinones, were isolated and characterized. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 4, pp. 804–809, April, 1997.