Polymerization of 2‐Substituted 2‐Oxazolines Induced by Photocationic Initiators

2‐Ethyl‐2‐oxazoline (EOZO) was polymerized using two different photocationic initiators: a combination of bis{(4‐diphenylsulfonium)phenyl}sulfide bis{hexafluoroantimonate} and (4‐phenyl sulfide)phenyl diphenylsulfonium hexafluoroantimonate (Cyracure UVI® 6974) and (η⁵‐2,4‐cyclopentadien‐1‐yl)‐[η⁶‐(1‐methylethyl)benzene]iron hexafluorophosphate (Irgacure® 261). The experimental data is consistent with the premise that in the presence of Cyracure UVI® 6974 the initiation proceeds via a Brønstedt acid. In the second case the generation of oxazolinium growing species is intermediated by a complex derived from the initial ferrocenium salt.     

Further Prenylated Bi‐ and Tricyclic Phloroglucinol Derivatives from Hypericum papuanum

From the petroleum‐ether extract of the dried aerial parts of Hypericum papuanum, three new prenylated tricyclic and four new bicyclic acylphloroglucinol derivatives were isolated by bioactivity‐guided fractionation. The structures of the bicyclic compounds enaimeone A, B, and C ( 1 / 1a , 2 / 2a , and 3 / 3a , resp.) were elucidated as rel‐(1R,5R,6S)‐4‐hydroxy‐6‐(1‐hydroxy‐1‐methylethyl)‐5‐methyl‐1‐(3‐methylbut‐2‐enyl)‐3‐(2‐methylpropanoyl)‐bicyclo[3.2.1]oct‐3‐ene‐2,8‐dione ( 1 / 1a ), rel‐(1R,5R,6R)‐4‐hydroxy‐6‐(1‐hydroxy‐1‐methylethyl)‐5‐methyl‐1‐(3‐methylbut‐2‐enyl)‐3‐(2‐methylpropanoyl)bicyclo[3.2.1]oct‐3‐ene‐2,8‐dione ( 2 / 2a ), rel‐(1R,5R,6R)‐4‐hydroxy‐6‐(1‐hydroxy‐1‐methylethyl)‐5‐methyl‐3‐(2‐methylbutanoyl)‐1‐(3‐methylbut‐2‐enyl)bicyclo[3.2.1]oct‐3‐ene‐2,8‐dione ( 3 / 3a ). The tricyclic isolates 8‐hydroxy‐3β‐(1‐hydroxy‐1‐methylethyl)‐4,4,7‐trimethyl‐9‐(2‐methylpropanoyl)‐5βH‐tricyclo[5.3.1.0^1,5]undec‐8‐ene‐10,11‐dione ( 4 ), 8‐hydroxy‐3α‐(1‐hydroxy‐1‐methylethyl)‐4,4,7‐trimethyl‐9‐(2‐methylpropanoyl)‐5βH‐tricyclo[5.3.1.0^1,5]undec‐8‐ene‐10,11‐dione ( 5 ), and 8‐hydroxy‐3α‐(1‐hydroxy‐1‐methylethyl)‐4,4,7‐trimethyl‐9‐(2‐methylbutanoyl)‐5βH‐tricyclo[5.3.1.0^1,5]undec‐8‐ene‐10,11‐dione ( 6 ), and their corresponding tautomers 4a , 5a , and 6a , were named 1′‐hydroxyialibinones A, B, and D, respectively. Oxidative decomposition of furonewguinone A (=2,3,3a,5‐tetrahydro‐3a‐hydroxy‐2‐(1‐hydroxy‐1‐methylethyl)‐5‐methyl‐5‐(3‐methylbut‐2‐enyl)‐7‐(2‐methylpropanoyl)‐benzofuran‐4,6‐dione; 7 ) led to furonewguinone B (=3,3a,7,7a‐tetrahydro‐3a,6,7a‐trihydroxy‐2‐(1‐hydroxy‐1‐methylethyl)‐7‐methyl‐7‐(3‐methylbut‐2‐enyl)‐5‐(2‐methylpropanoyl)benzofuran‐4(2H)‐one; 8 / 8a ). Structure elucidation was based on extensive 1D and 2D NMR studies, as well as on data derived from mass spectrometry. Furthermore, the cytotoxicity towards KB nasopharyngeal carcinoma cells and the antibacterial activity were determined.     

Structural analysis of an impurity of the drug landiolol

In a course of development and preparation of landiolol (1a), a known ultra‐short‐acting β‐blocker, process quality control by HPLC and LC‐MS analysis consistently showed an impurity peak ranging from 0.05% to 0.15 % and exhibiting a molecular mass m/z 887. To identify the hitherto unknown impurity, we prepared one of the possible landiolol derivatives with the same molecular mass for proper spectral characterization (NMR and MS). Its equivalence with the unknown impurity was then confirmed by LC‐MS analysis. Ultimately, using fragmentation patterns in LC‐MS and selective two‐dimensional NMR experiments, the structure of the impurity was assigned as [(4S)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl]methyl 3‐{4‐[(2S)‐2‐hydroxy‐3‐(3‐{4‐[(2S)‐2‐hydroxy‐3‐[(2‐{[(morpholin‐4‐yl)carbonyl]amino}ethyl)amino]propoxy]phenyl}‐N‐(2‐{[(morpholin‐4‐yl)carbonyl]amino}ethyl)propanamido)propoxy]phenyl}propanoate (2). It was found that the impurity was present in two rotameric forms at room temperature. The synthesis and NMR characterization of (2) are discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis,crystal structure studies and solvatochromic behaviour of two 2‐{5‐[4‐(dimethylamino)phenyl]penta‐2,4‐dien‐1‐ylidene}malononitrile derivatives

The synthesis, crystal structure studies and solvatochromic behavior of 2‐{(2E,4E)‐5‐[4‐(dimethylamino)phenyl]penta‐2,4‐dien‐1‐ylidene}malononitrile, C₁₆H₁₅N₃ (DCV[3]), and 2‐{(2E,4E,6E)‐7‐[4‐(dimethylamino)phenyl]hepta‐2,4,6‐trien‐1‐ylidene}malononitrile, C₁₈H₁₇N₃ (DCV[4]), are reported and discussed in comparison with their homologs having a shorter length of the π‐conjugated bridge. The compounds of this series have potential use as nonlinear materials with second‐order effects due to their donor–acceptor structures. However, DCV[3] and DCV[4] crystallized in the centrosymmetric space group P2₁/c which excludes their application as nonlinear optical materials in the crystalline state. They both crystallize with two independent molecules having the same molecular conformation in the asymmetric unit. The series DCV[1]–DCV[4] demonstrated reversed solvatochromic behavior in toluene, chloroform, and acetonitrile.     

Hydrogen‐bonding interactions in the 4‐aminobenzoic acid salt of atenolol monohydrate

Atenolol {or 4‐[2‐hydroxy‐3‐(isopropylamino)propoxy]phenylacetamide} crystallizes with 4‐aminobenzoic acid to give the salt {3‐[4‐(aminocarbonylmethyl)phenoxy]‐2‐hydroxypropyl}isopropylammonium 4‐aminobenzoate monohydrate, C₁₄H₂₃N₂O₃⁺·C₇H₆NO₂⁻·H₂O. In the crystal structure, the water molecule, the carboxylate group of 4‐aminobenzoate, and the hydroxy and ether O atoms of atenolol form a supramolecular R₃³(11) heterosynthon. Three other types of supramolecular synthons link the asymmetric unit into a two‐dimensional structure.     

Design,synthesis, in silico analysis with PPAR‐γ receptor and study of non‐covalent interactions in unsymmetrical heterocyclic/phenyl fleximer

This work deals with the design, synthesis, in silico analysis, crystallization, and the interpretation 2‐cyano‐3‐{4‐[2‐(phthalimid‐nyl)‐propoxy]‐phenyl}‐acrylic acid ethyl ester (7). Analog 7 is designed based on rosiglitazone. The quantitative analysis of Compound 7 has been performed through single‐crystal X‐Ray Diffraction (XRD) and Hirshfeld surface analysis. Fleximer 7 has studied the role of flexibility in non‐covalent interactions and binding affinity with PPAR‐γ receptors. Both phthalimide ring and phenyl rings are linked with propylene linker. 2‐cyano‐3‐{4‐[2‐(phthalimid‐nyl)‐propoxy]‐phenyl}‐acrylic acid ethyl ester has Z = 8 in the crystal packing and stabilized by intermolecular non‐covalent interactions like C? H…O, C? H…N, C? H…л, and л…л, and so forth.     

Speciation of phenyltin(IV) compounds using high‐performance liquid chromatography: Part 1. The direct analysis of mixed standard solutions of tetraphenyltin,triphenyltin chloride,triphenyltin hydroxide and triphenyltin acetate

A rapid speciation high‐performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of phenyltin compounds. The commercially important products of triphenyltin‐chloride, ‐acetate, ‐hydroxide and tetraphenyltin were separated by reversed‐phase HPLC on a Waters Spherisorb S5W ODS‐2 (octadecylsilica) column using an isocratic mixture of 90:10 (v/v) acetonitrile:water as the mobile phase at a flow rate of 1 ml min^?1. The phenyltin compounds were detected by UV detection at 254 nm and the total elution time is 8 min. The elution order is triphenyltin‐chloride, ‐acetate, ‐hydroxide and tetraphenyltin. Detection limits were 0.01 ppm for each of the triphenyltin compounds and 0.02 ppm for tetraphenyltin. Spiked water samples containing the three biocidal triphenyltin compounds could also be analysed simultaneously by the above method without the need for any prior derivatization, following extraction with toluene. The versatility of the method in sensing substituent group variations on the phenyl ring was also demonstrated by the successful resolution of the hydroxides, tris(p‐chlorophenyl)tin hydroxide, diphenyl(p‐chlorophenyl)tin hydroxide and triphenyltin hydroxide. Copyright © 2002 John Wiley & Sons, Ltd.     

Phenylethanoid Glycosides from the Roots of Digitalis ciliata Trautv.

Three new phenylethanoid glycosides, named digicilisides A – C ( 1  –  3 , resp.), have been isolated from the roots of Digitalis ciliata, along with five known phenylethanoid glycosides. The structures of 1  –  3 were identified as 2‐(4‐hydroxy‐3‐methoxyphenyl)ethyl β‐d ‐glucopyranosyl‐(1→3)‐[α‐l ‐rhamnopyranosyl‐(1→6)]‐4‐O‐[(E)‐feruloyl]‐β‐d ‐glucopyranoside ( 1 ), 2‐(3,4‐dihydroxyphenyl)ethyl α‐l ‐arabinopyranosyl‐(1→2)‐[β‐d ‐glucopyranosyl‐(1→3)]‐[α‐l ‐rhamnopyranosyl‐(1→6)]‐4‐O‐[(E)‐feruloyl]‐β‐d ‐glucopyranoside ( 2 ), and 2‐(3,4‐dihydroxyphenyl)ethyl β‐d ‐glucopyranosyl‐(1→3)‐{6‐O‐[(E)‐feruloyl]‐β‐d ‐glucopyranosyl‐(1→6)}‐4‐O‐[(E)‐caffeoyl]‐β‐d ‐glucopyranoside ( 3 ).     

Hansen solubility parameters for assay method optimization of simvastatin,ramipril, atenolol,hydrochlorothiazide and aspirin in human plasma using liquid chromatography with tandem mass spectrometry

A simple, specific, sensitive, validated method was developed using liquid chromatography with tandem mass spectrometry with electrospray ionization of human plasma for the simultaneous estimation of drugs (simvastatin, ramipril, atenolol, hydrochlorothiazide, and aspirin) of Polycap^TM capsule used in cardiovascular therapy. The interaction of these actives including internal standards between the stationary and mobile phase were investigated using Hansen solubility parameters. Chromatographic separation was performed on Phenomenex Synergi Polar‐RP (30 × 2 mm, 4 μm) column with a gradient mobile phase composition of acetonitrile and 5 mM ammonium formate for positive mode and 0.1% formic acid in both water and acetonitrile for negative mode. The flow rate and runtime were 1.0 mL/min and 3.5 min, respectively. Sample extraction was done by protein precipitation using acetonitrile, enabling a fast analysis. The calibration ranges from 0.1 to 100, 0.1 to 100, and 1 to 1000 ng/mL for simvastatin, ramipril, and atenolol using internal standard carbamazepine in positive mode, respectively, whereas it was 0.3–300 and 2–2000 ng/mL for hydrochlorothiazide and aspirin using internal standard 7‐hydroxy coumarin in negative mode, respectively. Hansen solubility parameters can be used as a high‐throughput optimizing tool for column and mobile phase selection in bioanalysis. This validated bioanalytical method has the potential for future fixed dose combination based preclinical and clinical studies that can save analysis time.     

On the Influence of the Carbohydrate Moiety on Chromophore Formation during Food‐Related Maillard Reactions of Pentoses,Hexoses, and Disaccharides

The influence of the carbohydrate moiety on the formation of 2‐[4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐en‐1‐ylidene]furan‐3(2H)‐one chromophores during food‐related Maillard reactions from pentoses, hexoses, and disaccharides is reported. The orange compounds 1a , b and 2a , b , detected in a roasted xylose/ L ‐proline mixture, were identified as (2E)/(2Z)‐4‐hydroxy‐5‐methyl‐2‐[4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐ene‐1‐ylidene]furan‐3(2H)‐one and (2E)/(2Z)‐5‐methyl‐2‐[4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐en‐1‐ylidene]‐4‐(pyrrolidin‐1‐yl)furan‐3(2H)‐one, respectively, by 1D‐ and 2D‐NMR, LC/mass, and UV/VIS spectroscopy, as well as by synthetic experiments. Studies on their formation revealed that 1a , b and 2a , b are formed upon condensation of pentose‐derived 4‐hydroxy‐5‐methyl‐ ( 3 ) and 5‐methyl‐4‐(pyrrolidin‐1‐yl)furan‐3(2H)‐one ( 4 ), respectively, with 2‐hydroxycyclopenta‐2,4‐dien‐1‐one ( 5 ) and L ‐proline (Scheme 1). Further condensation reaction of 1a , b with furan‐2‐carbaldehyde yielded the red (2Z)‐2‐{(5Z)‐5‐[(2‐furyl)methylidene]‐4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐en‐1‐ylidene}‐4‐hydroxy‐5‐methylfuran‐3(2H)‐one ( 6 ) as an additional novel Maillard chromophore. Replacement of the pentose by glucose in the mixture with L ‐proline led, after dry‐heating, to the identification of the structurally related colored (2Z)/(2E)‐2‐[5‐hydroxy‐5‐methyl‐4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐en‐1‐ylidene]‐4‐hydroxy‐5‐methylfuran‐3(2H)‐one ( 7a / 7b ) and to the characterization of 2,4,5‐trihydroxy‐5‐methylcyclopent‐2‐en‐1‐one ( 10 ) and 5‐hydroxy‐5‐methylcyclopent‐3‐ene‐1,2‐dione ( 11 ) as key intermediates in chromophore formation from hexoses. Comparative studies on disaccharides revealed that not 7a / 7b , but the colorless 4‐(α‐D ‐glucopyranosyloxy)‐2‐hydroxy‐2‐methyl‐6H‐pyran‐3(2H)‐one ( 8 ) and 2‐(α‐D ‐glucopyranosyloxy)‐4,5‐dihydroxy‐5‐methylcyclopent‐2‐en‐1‐one ( 9 ) were formed amongst the major degradation products of maltose (Scheme 4). The aglycons of 8 and 9 could not be liberated under food‐related heating conditions, thus, inhibiting the formation of the color precursors 10 and 11 and, in consequence, of 7a / 7b (Scheme 6). These data strongly suggest that the 1,4‐glycosidic linkage of disaccharides is responsible for their lower efficiency in browning development compared to pentoses or hexoses.     

Unexpected Imidazoquinoxalinone Annulation Products in the Photoinitiated Reaction of Substituted‐3‐Methyl‐Quinoxalin‐2‐Ones with N‐Phenylglycine

Photoinduced electron transfer between N ‐phenylglycine (NPG) and electronically excited triplets of 7‐substituted‐3‐methyl‐quinoxalin‐2‐ones in acetonitrile generate the respective ion radical pair, where by decarboxylation the phenyl‐amino‐alkyl radical, PhNHCH₂?, is generated. This radical reacts with the 3‐methyl‐quinoxalin‐2‐ones ground states, leading to the product 2. Other, unexpected, 7‐substituted‐1,2,3,3a‐tetrahydro‐3a‐methyl‐2‐phenylimidazo[1,5‐a]quinoxalin‐4(5H)‐ones, annulation products, 3a–f, were generated; likely by the addition of two PhNHCH₂? radicals, to positions 3 and 4 of the quinoxalin‐2‐ones. The reaction mechanism includes a photoinduced one electron transfer initiation step, propagation steps involving radical intermediates and NPG with radical chain termination steps that lead to the respective products 2a–f and 3a–f and NPG by‐products. The proposed mechanism accounts for the strong dependency found for the initial photoconsumption quantum yields on the electron‐withdrawing power of the substituent. Therefore, photolysis of common reactants widely used such as NPG and substituted quinoxalin‐2‐ones may provide a simple synthetic way to the unusual, unreported tetrahydro‐imidazoquinoxalinones 3a–f.     

Electrospray ionization mass spectrometry of tributyltin(IV) complexes and their larvicidal activity on mosquito larvae: crystal and molecular structure of polymeric (Bu3Sn[O2CC6H4{NN(C6H3‐4‐OH(C(H)NC6H4OCH3‐4))}‐o])n

A series of tributyltin(IV) complexes of 2‐[(E)‐2‐(3‐formyl‐4‐hydroxyphenyl)‐1‐diazenyl]benzoic acid and 4‐[((E)‐1‐{2‐hydroxy‐5‐[(E)‐2‐(2‐carboxyphenyl)‐1‐diazenyl]phenyl}methylidene)amino]aryls have been investigated by electrospray mass spectrometry (ESI‐MS) and tandem mass spectrometry (MSⁿ) techniques. The assignments are facilitated by agreement between observed and calculated isotopic patterns and MSⁿ studies. Single‐crystal X‐ray crystallography of (Bu₃Sn[O₂CC₆H₄{N?N(C₆H₃‐4‐OH(C(H)?NC₆H₄OCH₃‐4))}‐o])_n reveals a polymeric structure. Toxicity studies of the tributyltin(IV) complexes of the 4‐[((E)‐1‐{2‐hydroxy‐5‐[(E)‐2‐(2‐carboxyphenyl)‐1‐diazenyl]phenyl}methylidene)amino]aryls on the second larval instar of the Aedes aegypti and Anopheles stephensi mosquito larvae are also reported. The LC₅₀ values indicate that the complexes are effective larvicides, which range from a low of 0.36 ppm to a high of 0.69 ppm against the Ae. aegypti larvae and between 0.82 and 1.17 ppm against the An. stephensi larvae. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-[2-[<Superscript>18</Superscript>F]fluoro-3-(2-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazole-1-yl)propyl]tyrosine ([<Superscript>18</Superscript>F]FNT]) as a new class of tracer for imaging hypoxia

For detection of hypoxic tumor tissue, all radiotracers synthesized until now, are based on the concept that cellular uptake is being controlled by diffusion. As a new approach, we chose the concept to have the tracer hypothetically transported into the cells by well known carrier systems like the amino acid transporters. For this purpose, radiosynthesis of O-[2-[¹⁸F]fluoro-3-(2-nitro-1H-imidazole-1yl)propyl]tyrosine ([¹⁸F]FNT]) was carried out from methyl 2-(benzyloxycarbonyl)-3-(4-3-(2-nitro-1H-imidazol-1-yl)-2-(tosyloxy)propoxy) phenyl)propanoate via no-carrier-added nucleophilic aliphatic substitution. After labelling, 81 ± 0.9% of labelled intermediate i.e. methyl 2-(benzyloxycarbonyl)-3-(4-(2-[¹⁸F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propoxy) phenyl)propanoate was obtained at 140 °C. At the end of radiosynthesis, [¹⁸F]FNT was obtained in an overall radiochemical yield of 40 ± 0.9% (not decay corrected) within 90 min in a radiochemical purity of >98% in a formulation ready for application in the clinical studies for PET imaging of hypoxia.     

Two New 7‐Dehydrobrefeldin A Acids from Cylindrocarpon obtusisporum,an Endophytic Fungus of Trewia nudiflora

Two new 7‐dehydrobrefeldin A acids, (2E,4R*)‐4‐hydroxy‐4‐{(1R*,2S*)‐4‐oxo‐2‐[(1E)‐6‐oxohept‐1‐en‐1‐yl]cyclopentyl}but‐2‐enoic acid ( 3 ) and (2E,4R*)‐4‐hydroxy‐4‐{(1R*,2S*)‐2‐[(1E,6S*)‐6‐hydroxyhept‐1‐en‐1‐yl]‐4‐oxocyclopentyl}but‐2‐enoic acid ( 4 ), were isolated from the endophytic fungal strain Cylindrocarpon obtusisporum (Cooke & Harkness ) Wollenw . of Trewia nudiflora, together with two known compounds, 7‐dehydrobrefeldin A ( 2 ) and brefeldin A ( 1 ). Their structures were determined on the basis of extensive 1D‐ and 2D‐NMR‐spectral analysis.     

Structure elucidation of new acacic acid‐type saponins from Albizia coriaria

Three new acacic acid derivatives, named coriariosides C, D, and E ( 1–3 ) were isolated from the roots of Albizia coriaria. Their structures were elucidated on the basis of extensive 1D‐ and 2D‐NMR studies and mass spectrometry as 3‐O‐[β‐D ‐xylopyranosyl‐(1 → 2)‐β‐D ‐fucopyranosyl‐(1 → 6)‐2‐(acetamido)‐2‐deoxy‐β‐D ‐glucopyranosyl]‐21‐O‐{(2E,6S)‐6‐O‐{4‐O‐[(2E,6S)‐2,6‐dimethyl‐ 6‐O‐(β‐D ‐quinovopyranosyl)octa‐2,7‐dienoyl]‐4‐O‐[(2E,6S)‐2,6‐dimethyl‐6‐O‐(β‐D ‐quinovopyranosyl)octa‐2,7‐dienoyl]‐β‐D ‐quinovopyranosyl}‐2,6‐dimethylocta‐2,7‐dienoyl}acacic acid 28‐O‐β‐D ‐xylopyranosyl‐(1 → 4)‐α‐L ‐rhamnopyranosyl‐(1 → 2)‐β‐D ‐glucopyranosyl ester ( 1 ), 3‐O‐{β‐D ‐fucopyranosyl‐(1 → 6)‐[β‐D ‐glucopyranosyl‐(1 → 2)]‐β‐D ‐glucopyranosyl}‐21‐O‐{(2E,6S)‐6‐O‐{4‐O‐[(2E,6S)‐2,6‐dimethyl‐6‐O‐(β‐D ‐quinovopyranosyl)octa‐2,7‐dienoyl]‐4‐O‐[(2E,6S)‐2,6‐dimethyl‐6‐O‐(β‐D ‐quinovopyranosyl)octa‐2,7‐dienoyl]‐β‐D ‐quinovopyranosyl}‐2,6‐dimethylocta‐2,7‐dienoyl}acacic acid 28‐O‐α‐L ‐rhamno pyranosyl‐(1 → 2)‐β‐D ‐glucopyranosyl ester ( 2 ), and 3‐O‐[β‐D ‐fucopyranosyl‐(1 → 6)‐β‐D ‐glucopyranosyl]‐21‐O‐{(2E,6S)‐6‐O‐{4‐O‐[(2E,6S)‐2,6‐dimethyl‐6‐O‐(β‐D ‐quinovopyranosyl)octa‐2,7‐dienoyl)‐β‐D ‐quinovopyranosyl]octa‐2,7‐dienoyl}acacic acid 28‐O‐β‐D ‐glucopyranosyl ester ( 3 ). Copyright © 2010 John Wiley & Sons, Ltd.     

Three New Neolignans from the Aril of Myristica fragrans

Three new neolignans, named 1‐deoxycarinatone ( 1 ), isodihydrocarinatidin ( 2 ), and isolicarin A ( 3 ), together with the known neolignan (+)‐dehydrodiisoeugenol ( 4 ), were isolated from mace (the aril of Myristica fragrans Houtt .). Their structures were elucidated as 2‐[(1S)‐2‐(4‐hydroxy‐3‐methoxyphenyl)‐1‐methylethyl]‐6‐methoxy‐4‐(prop‐2‐enyl)phenol ( 1 ), 4‐[(2R,3R)‐2,3‐dihydro‐7‐methoxy‐3‐methyl‐5‐(prop‐2‐enyl)benzofuran‐2‐yl]‐2‐methoxyphenol ( 2 ), and 4‐{(2S,3R)‐2,3‐dihydro‐7‐methoxy‐3‐methyl‐5‐[(1E)‐prop‐1‐enyl]benzofuran‐2‐yl}‐2‐methoxyphenol ( 3 ) on the basis of spectroscopic data.     

Facile green one‐pot synthesis of novel thiazolo[3,2‐a]pyrimidine derivatives using Fe3O4@l‐arginine and their biological investigation as potent antimicrobial agents

Thiazolopyrimidine derivatives are well known because of their excellent therapeutic properties. In this investigation, an effective one‐pot three‐component method is described for the synthesis of novel 2‐[(Z )‐1‐(substituted phenyl)methylidine]‐7‐methyl‐3‐oxo‐5‐(substituted phenyl)‐2,3‐dihydro‐5H ‐thiazolo[3,2‐a]pyrimidine‐6‐carboxilic acid tert ‐butyl ester derivatives by condensation reaction of 3,4‐dihydropyrimidine‐2(1H )‐thiones, various aromatic aldehydes and chloroacetyl chloride under reflux conditions in the presence of Fe₃O₄@l ‐arginine nanoparticles as a magnetically reusable and eco‐friendly catalyst with short reaction times and moderate yields. The chemical structures of all synthesized compounds were determined using infrared, ¹H NMR and ¹³C NMR spectroscopies. In vitro antimicrobial activities of 3,4‐dihydropyrimidine‐2(1H )‐thiones and newly fused thiazolo[3,2‐a]pyrimidine derivatives were examined using the well diffusion method against diverse pathogenic strains, namely Staphylococcus aureus ATCC 6538, S. epidermidis ATCC 12228, Escherichia coli ATCC 8739 and Pseudomonas aeruginosa ATCC 9027 (bacteria), Candida albicans ATCC 10231 (yeast) and Aspergillus niger ATCC 16404 (fungus). The compounds having 2‐hydroxy, 4‐hydroxy, 2‐chloro and 4‐chloro groups attached to the phenyl ring on the pyrimidine and 4‐CH₃, 4‐OCH₃ and 3‐NO₂ groups attached to benzylidine on the thiazolo moiety showed significant antibacterial activity.     

Green One‐Pot Solvent‐Free Synthesis of Pyrazolo[1,5‐a]pyrimidines,Azolo[3,4‐d]pyridiazines,and Thieno[2,3‐b]pyridines Containing Triazole Moiety

Synthesis of pyrazolo[1,5‐a]pyrimidines, [1,2,4]triazolo[1,5‐a]pyrimidine, 8,10‐dimethyl‐2‐(5‐methyl‐1‐phenyl‐4,5‐dihydro‐1H‐1,2,3‐triazol‐4‐yl)pyrido[2′,3′:3,4]‐pyrazolo[1,5‐a]pyrimidine, benzo[4,5]imidazo[1,2‐a]pyrimidine via heterocyclic amines, and sodium 3‐hydroxy‐1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazole‐4‐yl)prop‐2‐en‐1‐one were carried out. Also, synthesis of isoxazoles, and pyrazoles from sodium 3‐hydroxy‐1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazole‐4‐yl)prop‐2‐en‐1‐one and hydroxymoyl chlorides and hydrazonoyl halides, respectively, were made. Analogously, (1,2,3‐triazol‐4‐yl)thieno[2,3‐b]pyridine derivatives were obtained from sodium 3‐hydroxy‐1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ triazole‐4‐yl)prop‐2‐en‐1‐one and cyanothioacetamide followed by its reacting with active methylene compounds. In addition to full characterization of all synthesized compounds, they were tested to evaluate their antimicrobial activities, and some compounds showed competitive activities to those of tetracycline, the typical antibacterial drug, and clotrimazole, the typical antifungal drug.     

Determination of PF‐04620110, a novel inhibitor of diacylglycerol acyltransferase‐1, in rat plasma using liquid chromatography–tandem mass spectrometry and its application in pharmacokinetic studies

In this study, we developed a method for the determination of PF‐04620110 (2‐{(1r,4r)‐4‐[4‐(4‐amino‐5‐oxo‐7,8‐dihydropyrimido[5,4‐f][1,4]oxazepin‐6(5H)‐yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT‐1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC‐MS/MS system for quantification. PF‐04620110 and imipramine (internal standard) were separated using a Hypersil Gold C₁₈ column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive‐ion mode [M + H]⁺ of multiple‐reaction monitoring were m/z 397.0 → 260.2 for PF‐04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF‐04620110 at concentrations within the range 0.05–50 µg/mL and the signal‐to‐noise ratios for the samples were ≥10. The intra‐ and inter‐day precision and accuracy of the method matched the acceptance criteria for assay validation. PF‐04620110 was stable under various processing and/or handling conditions. PF‐04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF‐04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

A simple synthesis of 5‐ethoxycarbonyl‐6‐phenyl‐1,3‐dioxin‐4‐ones and ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate

4‐Ethoxycarbonyl‐5‐phenyl‐2,3‐dihydrofuran‐2,3‐dione 1 reacts with aldehydes via the acylketene intermediate 2 giving the 1,3‐dioxin‐4‐ones 3a‐e and the 1,4‐bis(5‐ethoxycarbonyl‐4‐oxo‐6‐phenyl‐4H‐1,3‐dioxin‐2‐yl)benzene 4 , and a one step reaction between dibenzoylmethane and oxalylchloride gave 3,5‐dibenzoyl‐2,6‐diphenyl‐4‐pyrone 7 . The reaction of 1 with dibenzoylmethane, a dicarbonyl compound, provided ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate derivative 9 . Compound 9 was converted into the corresponding ethyl 3‐benzoyl‐4‐hydroxy‐2,6‐diphenylpyridine‐5‐carboxylate derivative 10 via its reaction with ammonium hydroxyde solution in 1 ‐butanol.