Synthesis and Cytotoxicity Evaluation of Metal‐Chelator‐Bearing Flavone,Carbazole, Dibenzofuran,Xanthone, and Anthraquinone

2‐(Aryloxymethyl)‐5‐benzyloxy‐1‐methyl‐1H‐pyridin‐4‐ones 8a – 8g , 2‐(aryloxymethyl)‐5‐hydroxy‐4H‐pyran‐4‐ones 9a – 9g , and 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a – 10g were prepared from the known 5‐benzyloxy‐2‐(hydroxymethyl)pyran‐4‐one ( 3 ) in a good overall yield. These compounds were evaluated in vitro against a three‐cell lines panel consisting of MCF7 (breast), NCI‐H460 (lung), and SF‐268 (CNS), and the active compounds passed on for evaluation in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results indicated that 5‐hydroxy derivatives are more favorable than their corresponding 5‐benzyloxy precursors ( 10a – 10g vs. 8a – 8g ), and 1‐methyl‐1H‐pyridin‐4‐ones are more favorable than their corresponding pyran‐4(1H)‐ones ( 10a – 10g vs. 9a – 9g ). Among these three types of compounds, 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a – 10g were the most cytotoxic; they inhibited the growth of almost all the cancer cells tested. On the contrary, compound 8a (a mean GI₅₀=27.8 μM ), 8b (38.5), 8d (11.0), and 8e (30.5) are especially active against the growth of SK‐MEL‐5 (a melanoma cancer cell) with a GI₅₀ of <0.01, 5.65, 0.55, and 0.03 μM , respectively (cf. Table 2).     

A Novel Synthetic Approach to (±)‐Desoxynoreseroline

(±)‐Desoxynoreseroline ( 3 ), the basic ring structure of the pharmacologically active alkaloid physostigmine ( 1 ), was synthesized starting from 3‐allyl‐1,3‐dimethyloxindole ( 9 ). The latter was prepared from the corresponding 2H‐azirin‐3‐amine 6 by a BF₃‐catalyzed ring enlargement via an amidinium intermediate 7 (Scheme 1). An alternative synthesis of 9 was also carried out by the reaction of N‐methylaniline with 2‐bromopropanoyl bromide ( 12 ), followed by intramolecular Friedel–Crafts alkylation of the formed anilide 13 to give Julian's oxindole 11 . Further alkylation of 11 with allyl bromide in the presence of LDA gave 9 in an excellent yield (Scheme 3). Ozonolysis of 9 , followed by mild reduction with (EtO)₃P, gave the aldehyde 14 , whose structure was chemically established by the transformation to the corresponding acetal 15 (Scheme 4). Condensation of 14 with hydroxylamine and hydrazine derivatives, respectively, gave the corresponding imine derivatives 16a – 16d as a mixture of syn‐ and anti‐isomers. Reduction of this mixture with LiAlH₄ proceeded by loss of ROH or RNH₂ to give racemic 3 (Scheme 5).     

Oligonucleotides Containing 7‐Deaza‐2′‐deoxyxanthosine: Synthesis,Base Protection,and Base‐Pair Stability

Oligonucleotides incorporating 7‐deaza‐2′‐deoxyxanthosine ( 3 ) and 2′‐deoxyxanthosine ( 1 ) were prepared by solid‐phase synthesis using the phosphoramidites 6 – 9 and 16 which were protected with allyl, diphenylcarbamoyl, or 2‐(4‐nitrophenyl)ethyl groups. Among the various groups, only the 2‐(4‐nitrophenyl)ethyl group was applicable to 7‐deazaxanthine protection being removed with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) by β‐elimination, while the deprotection of the allyl residue with Pd⁰ catalyst or the diphenylcarbamoyl group with ammonia failed. Contrarily, the allyl group was found to be an excellent protecting group for 2′‐deoxyxanthosine ( 1 ). The base pairing of nucleoside 3 with the four canonical DNA constituents as well as with 3‐bromo‐1‐(2‐deoxy‐β‐D ‐erythro‐pentofuranosyl)‐1H‐pyrazolo[3,4‐d]pyrimidine‐4,6‐diamine ( 4 ) within the 12‐mer duplexes was studied, showing that 7‐deaza‐2′‐deoxyxanthosine ( 3 ) has the same universal base‐pairing properties as 2′‐deoxyxanthosine ( 1 ). Contrary to the latter, it is extremely stable at the N‐glycosylic bond, while compound 1 is easily hydrolyzed under slightly acidic conditions. Due to the pK_a values 5.7 ( 1 ) and 6.7 ( 3 ), both compounds form monoanions under neutral conditions (95% for 1 ; 65% for 3 ). Although both compounds form monoanions at pH 7.0, pH‐dependent T_m measurements showed that the base‐pair stability of 7‐deaza‐2′‐deoxyxanthosine ( 3 ) with dT is pH‐independent. This indicates that the 2‐oxo group is not involved in base‐pair formation.     

A New Route to Vitamin E Key‐Intermediates by Olefin Cross‐Metathesis

Ru‐Catalyzed olefin cross‐metathesis (CM) has been successfully applied to the synthesis of several phytyl derivatives ( 2b, 2d – f, 3b ) with a trisubstituted C?C bond, as useful intermediates for an alternative route to α‐tocopheryl acetate (vitamin E acetate; 1b ) (Scheme 1). Using the second‐generation Grubbs catalyst RuCl₂(C₂₁H₂₆N₂)(CHPh)PCy₃ (Cy = cyclohexyl; 4a ) and Hoveyda–Grubbs catalyst RuCl₂(C₂₁H₂₆N₂){CH‐C₆H₄(O‐ⁱPr)‐2} ( 4b ), the reactions were performed with various C‐allyl ( 5a – f, 7a,b ) and O‐allyl ( 8a – d ) derivatives of trimethylhydroquinone‐1‐acetate as substrates. 2,6,10,14‐Tetramethylpentadec‐1‐ene ( 6a ) and derivatives 6c – e of phytol ( 6b ) as well as phytal ( 6f ) were employed as olefin partners for the CM reactions (Schemes 2 and 5). The vitamin E precursors could be prepared in up to 83% isolated yield as (E/Z)‐mixtures.     

Calcium-mediated dearomatization, C-H bond activation, and allylation of alkylated and benzannulated pyridine derivatives

A facile and general synthetic pathway for the production of dearomatized, allylated, and C? H bond activated pyridine derivatives is presented. Reaction of the corresponding derivative with the previously reported reagent bis(allyl)calcium, [Ca(C₃H₅)₂] ( 1 ), cleanly affords the product in high yield. The range of N‐heterocyclic compounds studied comprised 2‐picoline ( 2 ), 4‐picoline ( 3 ), 2,6‐lutidine ( 4 ), 4‐tert‐butylpyridine ( 5 ), 2,2′‐bipyridine ( 6 ), acridine ( 7 ), quinoline ( 8 ), and isoquinoline ( 9 ). Depending on the substitution pattern of the pyridine derivative, either carbometalation or C? H bond activation products are obtained. In the absence of methyl groups ortho or para to the nitrogen atom, carbometalation leads to dearomatized products. C(sp³)? H bond activation occurs at ortho and para situated methyl groups. Steric shielding of the 4‐position in pyridine yields the ring‐metalated product through C(sp²)? H bond activation instead. The isolated compounds [Ca(2‐CH₂‐C₅H₄N)₂(THF)] ( 2 b ?(THF)), [Ca(4‐CH₂‐C₅H₄N)₂(THF)₂] ( 3 b ?(THF)₂), [Ca(2‐CH₂‐C₅H₃N‐6‐CH₃)₂(THF)_n] ( 4 b ?(THF)_n; n=0, 0.75), [Ca{2‐C₅H₃N‐4‐C(CH₃)₃}₂(THF)₂] ( 5 c ?(THF)₂), [Ca{4,4′‐(C₃H₅)₂‐(C₁₀H₈N₂)}(THF)] ( 6 a ?(THF)), [Ca(NC₁₃H₉‐9‐C₃H₅)₂(THF)] ( 7 a ?(THF)), [Ca(4‐C₃H₅‐C₉H₇N)₂(THF)] ( 8 b ?(THF)), and [Ca(1‐C₃H₅‐C₉H₇N)₂(THF)₃] ( 9 a ?(THF)₃) have been characterized by NMR spectroscopy and metal analysis. 9 a ?(THF)₄ and 4 b ?(THF)₃ were additionally characterized in the solid state by X‐ray diffraction experiments. 4 b ?(THF)₃ shows an aza‐allyl coordination mode in the solid state. Based on the results, mechanistic aspects are discussed in the context of previous findings.     

Selbstorganisation von Chinodimethanen über kovalente Bindungen,Mitteilung III,Untersuchungen zur Herstellung von Nanostrukturen

Self‐Assembly of Quinodimethanes through Covalent Bonds. Part III. Investigations on the Preparation of Nanostructures As part of our studies on the tetramerization of quinodimethane 1 to the macrocyclic compound 2 , the influence of substituents on this reaction was investigated. It was found that a large range of substituents such as 2‐phenylethyl, 2‐(4‐methoxyphenyl)ethyl, 2‐(4‐fluorophenyl)ethyl, 2‐[4‐(tert‐butyl)phenyl]ethyl, and 2‐[4‐(2‐phenylethyl)phenyl]ethyl, attached at positions 2 and 7 of 9H‐fluorene, do not prevent the tetramerization. The key step in the formation of the macrocylic compounds 13a – e is the debromination of 12a – e with mercury to the corresponding quinodimethanes which undergo a self‐assembly forming 13a – e in high yields. To study the conjugative influence of substituents on tetramerization, the effect of the hex‐1‐ynyl groups at positions 3 and 6 of the 9H‐fluorene rings was investigated. In this case, the corresponding macrocycle 17 was generated by the reaction of diol 16a with SnCl₂. Although the expected tetramerization to 17 occurred, the yield was lower than in the case of 13a – e , due to the sensitivity of the product.     

Nitrogen‐Rich Compounds of the Lanthanoids: The 5,5′‐Azobis[1H‐tetrazol‐1‐ides] of some Yttric Earths (Tb,Dy, Ho,Er, Tm,Yb, and Lu)

A set of N‐rich salts, 3 – 9 , of the heavy lanthanoids (terbium, 3 ; dysprosium, 4 ; holmium 5 ; erbium, 6 ; thulium, 7 ; ytterbium, 8 ; lutetium, 9 ) based on the energetic 5,5′‐azobis[1H‐tetrazole] (H₂ZT) was synthesized and characterized by elemental analysis, vibrational (IR and Raman) spectroscopy, and X‐ray structure determination. The synthesis of the lanthanoid salts 3 – 9 was performed by crystallization from concentrated aqueous solutions of disodium 5,5′‐azobis[1H‐tetrazol‐1‐ide] dihydrate (Na₂ZT?2 H₂O; 1 ) and the respective Ln(NO₃)₃?5 H₂O and yielded large rhombic crystals of the type [Ln(H₂O)₈]₂(ZT)₃?6 H₂O in ca. 70% of the theoretical yield. The compounds 3 – 9 are isostructural (triclinic space group P ) to the previously published yttrium salt 2 ; they show, however, a clear lanthanoid contraction of several crystallographic parameters, e.g., the cell volume or the Ln? O bond lengths of the Ln³⁺ ions and the coordinating H₂O molecules. The lanthanoid contraction influences the strengths of the H‐bonds, which can be observed as a red shift by 4 cm^?1 in the characteristic IR band, in particular from 3595 cm^?1 ( 3 ) to 3599 cm^?1 ( 9 ). In good agreement with previous works, 2 – 9 are purely salt‐like compounds without a coordinative bond between the tetrazolide anion and the Ln³⁺ cation.     

A Novel Synthesis of 4‐Pyridazineacetic Acids via Ring Expansion of N‐Cyanomethylated 3‐Pyrazoline‐4‐acetic Acids

A novel synthetic route to 4‐pyridazineacetic acids 10 – 12 has been achieved by the ring‐expansion reaction of N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 – 9 . 1H‐Pyrazole‐4‐acetic acids 1 – 3 were reacted with iodoacetonitrile in the presence of triethylamine in refluxing acetonitrile to give the corresponding C‐cyanomethylated 1H‐pyrazole‐4‐acetic acids 4 – 6 as major products together with N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 8 as minor products. On the other hand, reactions of 1 and 3 with chloroacetonitrile in the presence of triethylamine in refluxing chloroform afforded the corresponding N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 9 as major products. Thermal treatment of 7 – 9 with sodium hydride in N,N‐dimethylformamide caused ring expansion to yield the corresponding 4‐pyridazineacetic acids 10 – 12 .     

Synthesis,Antiviral, and Antimicrobial Activity of N‐ and S‐Alkylated Phthalazine Derivatives

A series of N‐alkylphthalazinone were synthesized by the reaction of phthalazin‐1(2H)‐one derivatives 1a , 1b , 1c with alkylating agents namely, propargyl, allyl bromide, epichlorohydrin, 1,3‐dichloro‐2‐propanol, 4‐bromobutylacetate, and 1‐(bromomethoxy)ethyl acetate to give the corresponding N‐alkylphthalazinone 2a , 2b , 2c , 3a , 3b , 3c , 5a , 5b , 5c , 6a , 6b , 6c , 7a , 7b , 7c , and 9a , 9b , 9c . Alkylation of phthalazin‐1(2H)‐thione to give a series from S‐alkylphthalazine 12 , 13 , 14 and thioglycosides 15 and 17 was performed. Deprotection of compounds 7a , 7b , 7c , 9a , 9b , 9c , 15 , and 17 resulted in the formation of the corresponding products 8a , 8b , 8c , 10a , 10b , 10c , 16 , and 18 . The structure of newly synthesized compounds was assigned by IR, ¹H, ¹³C NMR, and elemental analysis. Some of these compounds were screened for antiviral and antimicrobial activity.     

Rare‐Earth‐Metal–Hydrocarbyl Complexes Bearing Linked Cyclopentadienyl or Fluorenyl Ligands: Synthesis,Catalyzed Styrene Polymerization,and Structure–Reactivity Relationship

A series of rare‐earth‐metal–hydrocarbyl complexes bearing N‐type functionalized cyclopentadienyl (Cp) and fluorenyl (Flu) ligands were facilely synthesized. Treatment of [Y(CH₂SiMe₃)₃(thf)₂] with equimolar amount of the electron‐donating aminophenyl‐Cp ligand C₅Me₄H‐C₆H₄‐o‐NMe₂ afforded the corresponding binuclear monoalkyl complex [({C₅Me₄‐C₆H₄‐o‐NMe(μ‐CH₂)}Y{CH₂SiMe₃})₂] ( 1 a ) via alkyl abstraction and C? H activation of the NMe₂ group. The lutetium bis(allyl) complex [(C₅Me₄‐C₆H₄‐o‐NMe₂)Lu(η³‐C₃H₅)₂] ( 2 b ), which contained an electron‐donating aminophenyl‐Cp ligand, was isolated from the sequential metathesis reactions of LuCl₃ with (C₅Me₄‐C₆H₄‐o‐NMe₂)Li (1 equiv) and C₃H₅MgCl (2 equiv). Following a similar procedure, the yttrium‐ and scandium–bis(allyl) complexes, [(C₅Me₄‐C₅H₄N)Ln(η³‐C₃H₅)₂] (Ln=Y ( 3 a ), Sc ( 3 b )), which also contained electron‐withdrawing pyridyl‐Cp ligands, were also obtained selectively. Deprotonation of the bulky pyridyl‐Flu ligand (C₁₃H₉‐C₅H₄N) by [Ln(CH₂SiMe₃)₃(thf)₂] generated the rare‐earth‐metal–dialkyl complexes, [(η³‐C₁₃H₈‐C₅H₄N)Ln(CH₂SiMe₃)₂(thf)] (Ln=Y ( 4 a ), Sc ( 4 b ), Lu ( 4 c )), in which an unusual asymmetric η³‐allyl bonding mode of Flu moiety was observed. Switching to the bidentate yttrium–trisalkyl complex [Y(CH₂C₆H₄‐o‐NMe₂)₃], the same reaction conditions afforded the corresponding yttrium bis(aminobenzyl) complex [(η³‐C₁₃H₈‐C₅H₄N)Y(CH₂C₆H₄‐o‐NMe₂)₂] ( 5 ). Complexes 1 – 5 were fully characterized by ¹H and ¹³C NMR and X‐ray spectroscopy, and by elemental analysis. In the presence of both [Ph₃C][B(C₆F₅)₄] and AliBu₃, the electron‐donating aminophenyl‐Cp‐based complexes 1 and 2 did not show any activity towards styrene polymerization. In striking contrast, upon activation with [Ph₃C][B(C₆F₅)₄] only, the electron‐withdrawing pyridyl‐Cp‐based complexes 3 , in particular scandium complex 3 b , exhibited outstanding activitiy to give perfectly syndiotactic (rrrr >99 %) polystyrene, whereas their bulky pyridyl‐Flu analogues ( 4 and 5 ) in combination with [Ph₃C][B(C₆F₅)₄] and AliBu₃ displayed much‐lower activity to afford syndiotactic‐enriched polystyrene.     

Synthesis,Structure, and Photophysical Properties of the Di‐ and Trinuclear Phosphine‐Diimine Complexes of Copper(I)

Reactions of [Cu(NCMe)₄]⁺ with stoichiometric amount of diphosphine R₂P–(C₆H₄)_n–PR₂, (R = NC₄H₄, n = 1; R = Ph, n = 1, 2, 3) or tri‐phosphine 1, 3, 5‐(PPh₂–C₆H₄–)₃–C₆H₃ ligands give the corresponding di‐ or trinuclear copper(I) acetonitrile‐phosphine complexes 1 – 5 . Substitution of the labile acetonitrile groups with chelating aromatic diimines – 2, 2′‐bipyridine (bpy), 1, 10‐phenanthroline (phen), 5, 6‐dimethyl‐1, 10‐phenanthroline (dmp), 5, 6‐dibromo‐1, 10‐phenanthroline (phenBr₂) – gives the corresponding substituted compounds 6 – 16 . In all complexes 1 – 16 each central Cu^I atom has tetrahedral configuration completed with two N‐ and two P‐donor groups. The compounds obtained were characterized using elemental analysis, ESI‐MS, X‐ray crystallography, and NMR spectroscopy. All phosphine‐diimine compounds 6 – 16 are photoluminescent at room temperature both in dichloromethane solution and in solid state (λ_ex = 385 nm). In CH₂Cl₂ solution the maxima of emission bands are found in a range 540–640 nm, and in solid in a similar range 538–620 nm. Emission of 6 – 16 is assigned to the triplet excited state dominated by the charge transfer transitions with contribution of the MLCT character.     

Syntheses,Structures, Magnetic Properties,and NIR Emission Properties of a Series of Novel 1, 2, 4, 5‐Cyclohexanetetracarboxylate‐bridged Lanthanide Complexes with 3D Framework Structures

Solvothermal combination of trivalent lanthanide metal precursors with 1, 2, 4, 5‐cyclohexanetetracarboxylic acid (L) ligand has afforded the preparation of a family of eight new coordination polymers [Ln₄(L)₃(H₂O)₁₀] · 7H₂O (Ln = Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb) ( 1 – 8 ). Structural analyses reveal that the 1, 2, 4, 5‐cyclohexanetetracarboxylic acid ligand with e,a,a,e (L^I) conformation displays a μ₄‐(κ³O, O, O⁵)(κ²O²,O²)(κ²O⁴,O⁴)‐bridging mode to generate 3D frameworks of complexes 1 – 8 and the α‐Po topology with the short Schläfli symbol {4¹².6³} could be observed in complexes 1 – 8 . The near‐infrared luminescence properties were studied, and the results have shown that the Ho^III, Er^III, and Yb^III complexes emit typical near‐infrared luminescence in the solid‐state. Variable‐temperature magnetic susceptibility measurements of complexes 2 – 7 have shown that complex 2 (Gd) shows the ferromagnetic coupling between magnetic centers, whereas the complexes 3 – 7 show the antiferromagnetic coupling between magnetic centers. Additionally, the thermogravimetric analyses were discussed.     

Pericyclic Transformations at the Periphery of Chromen‐4‐one (=4H‐1‐Benzopyran‐4‐one): An Unusual Preference for a 1,5‐Shift of Allylic Moieties over the Ene Reaction

Quite unlike the reported facile ene reactions on the periphery of many related heterocyclic systems, similarly disposed moieties on the periphery of the chromen‐4‐one (=4H‐1‐benzopyran‐4‐one) system fail to undergo an ene reaction and display a rather unusual preference for an overall [1,5] shift of the allylic C‐atom. Thus, heating xylene solutions of 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, and 2‐(N‐cinnamylamino)‐substituted (E)‐(oxochromenyl)propenoates 9a – c and 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted (E)‐(oxochromenyl)propenoates 16a – c in a sealed tube at 220–230° leads to a [1,5] shift of the allylic moieties (allyl, crotyl, cinnamyl), which is followed by intramolecular cyclization involving the N‐atom and the ester function, to give the 3‐allyl‐3‐crotyl‐, and 3‐cinnamyl‐substituted‐1‐phenyl‐ or 1‐benzyl‐2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 10a – c and 17a – c . The anticipated carbonyl–ene reaction in the 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, 2‐(N‐cinnamylanilino)‐, 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted 4‐oxochromene‐3‐carboxaldehydes 8a – c and 15a – c is also not observed, and these molecules remain untransformed under identical conditions. No [1,5] shifts of benzyl, phenyl, or methyl groups are observed, even in the absence of allylic moieties, though facile [1,5]‐H shift occurs in 2‐(benzylamino)‐ and 2‐(phenylamino)‐substituted (E)‐(oxochromenyl)propenoates 23a , b , which is followed by a similar intramolecular cyclization leading to the 2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 24a , b .     

Synthesis of 9‐Halogenated 9‐Deazaguanine N7‐(2′‐Deoxyribonucleosides)

The syntheses of N⁷‐glycosylated 9‐deazaguanine 1a as well as of its 9‐bromo and 9‐iodo derivatives 1b , c are described. The regioselective 9‐halogenation with N‐bromosuccinimide (NBS) and N‐iodosuccinimide (NIS) was accomplished at the protected nucleobase 4a (2‐{[(dimethylamino)methylidene]amino}‐3,5‐dihydro‐3‐[(pivaloyloxy)methyl]‐4H‐pyrrolo[3,2‐d]pyrimidin‐4‐one). Nucleobase‐anion glycosylation of 4a – c with 2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D ‐erythro‐pentofuranosyl chloride ( 5 ) furnished the fully protected intermediates 6a – c (Scheme 2). They were deprotected with 0.01M NaOMe yielding the sugar‐deprotected derivatives 8a – c (Scheme 3). At higher concentrations (0.1M NaOMe), also the pivaloyloxymethyl group was removed to give 7a – c , while conc. aq. NH₃ solution furnished the nucleosides 1a – c . In D₂O, the sugar conformation was always biased towards S (67–61%).     

Bioactive Heteroleptic Bismuth(V) Complexes: Synthesis,Structural Analysis and Binding Pattern Validation

Heteroleptic triorganobismuth (V) complexes of general formula, R₃Bi(OOCR')₂ ( 1 – 7 ), where R = C₆H₅ ( 1 – 3 ), p‐CH₃C₆H₄ ( 4 – 7 ) and R' = 3,5‐Cl₂C₆H₃ ( 1 , 5 ); 3,4,5‐(OCH₃)₃C₆H₂ ( 2 , 6 ); 3‐CH₃C₆H₄ ( 3 , 7 ); 2‐OH‐3‐OCH₃C₆H₃ ( 4 ) have been synthesized and fully characterized by FT‐IR, ¹H &¹³C NMR spectroscopy, single crystal X‐ray crystallography and elemental analysis. The molecular geometry observed for the compounds is predominantly distorted trigonal bipyramidal, the fact which was subsequently authenticated through X‐ray analyses for ( 1 – 4 ). All the synthesized compounds have been bio‐assayed for antileishmanial (Leishmania tropica KWH23) and Jack beans urease inhibitory activity, and human Lymphocytes were used to measure the general toxicity. Of these, ( 4 ) proved to be highly effective against the target species (Leishmania tropica KWH23), while being non‐toxic towards the mammalian cells at levels below 0.74 μgmL^?1, making it highly promising drug candidate. The high activities for ( 2 , 4 , and 6 ) against Jack beans Urease as compared to the reference standard demonstrate their significance in searching of therapeutic agents in future programs. The significant binding score of ( 2 & 4 ) against H. pylori in molecular docking studies further revealed their importance in future drug discovery processes.     

Synthesis and Characterization of New Thebaine Derivatives as Potential Opioid Agonists and Antagonists: 2‐[N‐(1H‐Tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazoles

In this study, we report the synthesis a series of novel 2‐[N‐(1H‐tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazole derivatives ( 7a – e ) which have potential opioid antagonist and agonist. The substitution reaction of 6,14‐endo‐ethenotetrahydrothebaine‐7α‐carbohydrazide with corresponding benzoyl chlorides gave diacylhydrazine compounds 4a – e in good yields. The treatment of compounds 4a – e with POCl₃ caused the conversion of side‐chain of compounds 5a – e into 1,3,4‐oxadiazole ring at C(7) position; thus, compounds 5a – e were obtained. Subsequently, cyanamides ( 6a – e ) were prepared from compounds 5a – e and then compounds 7a – e were synthesized by the azidation of 6a – e with NaN₃. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C APT, 2D‐NMR (COSY, NOESY, HMQC, HMBC) and high‐resolution mass spectral data.     

Polymer complexes. LXX. Synthesis,spectroscopic studies,thermal properties and antimicrobial activity of metal(II) polymer complexes

The monomer 3‐allyl‐5‐(phenylazo)‐2‐thioxothiazolidine‐4‐one (HL) was prepared by the reaction of allyl rhodanine with aniline through diazo‐coupling reaction. Reaction of HL with Ni(II) or Co(II) salts gave polymer complexes ( 1 – 8 ) with general stoichiometries [M(HL)(Cl)₂(OH₂)₂]_n, [M(HL)(O₂SO₂)(OH₂)₂]_n, [M(L)(O₂NO)(H₂O)₂]_n and [M(L)(O₂CCH₃)(H₂O)₂]_n (where M = Ni(II) or Co(II)). The structures of the polymer complexes were identified using elemental analysis, infrared and electronic spectra, molar conductance, magnetic susceptibility, X‐ray diffraction and thermogravimetric analysis. The interaction between the polymer complexes and calf thymus DNA showed a hypochromism effect. HL and its polymer complexes were tested against bacterial and fungal species. Co(II) polymer complex 2 is the most effective against Klebsiella pneumoniae and is more active than penicillin. The results showed that Ni(II) polymer complex 5 is a good antibacterial agent against Staphylococcus aureus and Pseudomonas aeruginosa. Molecular docking was used to predict the binding between the monomer with the receptors of prostate cancer (PDB code: 2Q7L Hormone) and breast cancer (PDB code: 1JNX Gene regulation). Coats–Redfern and Horowitz–Metzger methods were applied for calculating the thermodynamic parameters of HL and its polymer complexes. The thermal activation energy of decomposition for HL is higher than that for the polymer complexes.     

7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine,and 2′‐Deoxyisoguanosine: Syntheses and Properties

A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9H‐purine ( 11a ) with Selectfluor (Scheme 1). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9H‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e (Scheme 2). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 (Scheme 6). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction (Scheme 5). The pK_a values of the halogenated nucleosides were determined (Table 3). ¹³C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents (Fig. 3). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population (Fig. 2 and Table 1).     

Synthesis,structure and in vitro cytotoxicity of platinum(II) complexes containing eugenol and a quinolin‐8‐ol‐derived chelator

The synthesis of potassium (η²‐4‐allyl‐2‐methoxyphenol)trichloridoplatinate(II), K[PtCl₃(C₁₀H₁₂O₂)], ( 1 ), starting from Zeise's salt and Ocimum sanctum L. oil has been optimized. Starting from ( 1 ), three new platinum(II) complexes, namely (η²‐4‐allyl‐2‐methoxyphenol)chlorido(2‐methylquinolin‐8‐olato‐κ²N ,O )platinum(II), ( 2 ), (η²‐4‐allyl‐2‐methoxyphenol)chlorido(5‐nitroquinolin‐8‐olato‐κ²N ,O )platinum(II), ( 3 ), and (η²‐4‐allyl‐2‐methoxyphenol)chlorido(5,7‐dichloroquinolin‐8‐olato‐κ²N ,O )platinum(II), [Pt(C₉H₄Cl₂NO)Cl(C₁₀H₁₂O₂)], ( 4 ), containing eugenol and a quinolin‐8‐ol derivative (R‐OQ), have been synthesized and characterized by elemental analyses, MS, IR, ¹H NMR and NOESY spectra. For ( 1 ) and ( 4 ), single‐crystal X‐ray diffraction studies were also carried out. Complexes ( 2 )–( 4 ) show good inhibiting abilities on three human cancer cell lines, i.e. KB, Hep‐G2 and LU, with IC₅₀ values of 1.42–17.8 µM . Complex ( 3 ) gives an impressively high activity against KB, Hep‐G2, LU and MCF‐7, with IC₅₀ values of 1.42–4.91 µM , which are much lower than those of cisplatin and some other platinum(II) complexes.     

1, 9‐Dihydro‐purine‐6‐thione Derivatives of the d8–d10 Metal Ions (PdII,PtII, and CuI): Synthesis,Spectroscopy, and Structures

Reaction of 1, 9‐dihydro‐purine‐6‐thione (puSH₂) in presence of aqueous sodium hydroxide with PdCl₂(PPh₃)₂ suspended in ethanol formed [Pd(κ²‐N⁷,S‐puS)(PPh₃)₂] ( 1 ). Similarly, complexes [Pd(κ²‐N⁷,S‐puS)(κ²‐P, P‐L‐L)] ( 2 – 4 ) {L‐L = dppm (m = 1) ( 2 ), dppp (m = 3) ( 3 ), dppb (m = 4) ( 4 )} were prepared using precursors the [PdCl₂(L‐L)] {L‐L = Ph₂P–(CH₂)_m–PPh₂}. Reaction of puSH₂ suspended in benzene with platinic acid, H₂PtCl₆, in ethanol in the presence of triethylamine followed by the addition of PPh₃ yielded the complex [Pt(κ²‐N⁷,S‐puS)(PPh₃)₂] ( 5 ). Complexes [Pt(κ²‐N⁷,S‐puS)(κ²‐P, P‐L‐L)] ( 6 – 8 ) {L‐L = dppm ( 6 ), dppp ( 7 ), dppb ( 8 )} were prepared similarly. The 1, 9‐dihydro‐purine‐6‐thione acts as N⁷,S‐chelating dianion in compounds 1 – 8 . The reaction of copper(I) chloride [or copper(I) bromide] in acetonitrile with puSH₂ and the addition of PPh₃ in methanol yielded the same product, [Cu(κ²‐N⁷,S‐puSH)(PPh₃)₂] ( 9 ), in which the halogen atoms are removed by uninegative N, S‐chelating puSH^– anion. However, copper(I) iodide did not lose iodide and formed the tetrahedral complex, [CuI(κ¹‐S‐puSH₂)(PPh₃)₂] ( 10 ), in which the thio ligand is neutral. These complexes were characterized with the help of elemental analysis, NMR spectroscopy (¹H, ³¹P), and single‐crystal X‐ray crystallography ( 3 , 7 , 8 , 9 , and 10 ).