Synthesis of l-azaisotryptophan and its analogs: a general access to new 2-substituted azaindoles

l-(N-Cbz)-7-azaisotryptophan, l-(N-Cbz)-1a, a new isostere of tryptophan, was synthesized by reacting Li₂-(N-Boc)-2-amino-3-picoline, Li₂-(N-Boc)-2a, with appropriately protected l-aspartic acid followed by simple functional group manipulation. This synthetic success led us to access a set of analogs of azaisotryptophan (4a–c; 6a–c) as well as a new class of chiral amines (7a–c; 8a–c) for future application in asymmetric synthesis and design of homochiral ligands. Further, we have generalized the method substantiating a variety of new azaindol-2-yl derivatives (10aa–10lc) with functionalized substituents. In a preliminary luminescence characterization, l-(N-Cbz)-1a has exhibited about 30 nm bathochromic shifted fluorescence emission compared to tryptophan and (N-Cbz)-tryptophan.     

Half-sandwich η-arene–ruthenium(II) complexes bearing 1-alkyl(benzyl)-imidazo[4,5-f][1,10]-phenanthroline (IP) derivatives: the effect of alkyl chain length of ligands to catalytic activity

The reaction of bromoalkanes (R–Br; (3), R=C_nH_2n+1, n=4 (a), 8 (b), 12 (c),18 (d)) and bromobenzyl derivatives (R′–Br; (4), R′=CH₂C₆H₂(CH₃)₃-2,4,6 (a); CH₂C₆H(CH₃)₄-2,3,5,6 (b); CH₂C₆(CH₃)₅ (c)) with 1H-imidazo[4,5-f][1,10]-phenanthroline (IP)(L₂) gave the corresponding 1-R-imidazo[4,5-f][1,10]-phenanthroline (IPR)(L_3a–d) and 1-R′-imidazo[4,5-f][1,10]-phenanthroline(IPR')(L_4a–c) ligands, respectively. Treatment of L_3a–d and L_4a–d with [Ru(p-cymene)Cl₂]₂ led to the formation of [Ru(p-cymene)(IPR)Cl]Cl (RuL_3a–d) and [Ru(p-cymene)(IPR′)Cl]Cl (RuL_4a–c). New ruthenium(II) complexes RuL_3a–d and RuL_4a–c were characterized by elemental analysis, FTIR, UV–visible and NMR spectroscopy. In order to understand effects of these changes on the N-substituent of imidazol on IP and how they translate to catalytic activity, these new RuL₂, RuL_3a–d and RuL_4a–c were applied in the transfer hydrogenation of ketones by 2-propanol in presence of potassium hydroxide. The activities of the catalysts were monitored by NMR and GC analysis.     

Structurally original oxathioethers macrocycles containing an exocyclic double-bond: synthesis,characterization, reactivity,and coordination

New oxathioethers macrocycles have been synthesized and characterized. Each macrocycle consists in structurally defined ether and thioether moieties and an exocyclic double-bond (2a–c) or a hydroxymethyl group (3a–c). Macrocycles (2a–c) have been synthesized by reaction of dianions of thioethers diols (1a–c) with 3-chloro-2-chloromethylprop-1-ene. Their hydroboration/oxidation led to corresponding primary alcohols (3a–c). Structures of compounds (2b) and (3a) have been determined by X-ray diffraction. The reactivity of the hydroxyl group allowed the preparation of oxathioethers macrocycles bearing a polyether chain or a benzyl group (4a,b) and the synthesis of new bicyclic sandwich-type compounds (5a,b). The ability of these functionalized macrocycles to coordinate to palladium has been investigated.     

An unexpected formation of pyrazolopyrimidines during the attempted to obtain 5-substituted tetrazoles from carbonitriles

In this Letter, we described the synthesis of new 5-(5-amino-1-aryl-1H-pyrazole-4-yl)-1H-tetrazoles 2a–c from 5-amino-1-aryl-1H-pyrazole-4-carbonitriles 1a–c as well as the unexpected 1H-pyrazolo[3,4-d]pyrimidine derivatives 6a–c from 5-amino-1-aryl-3-methyl-1H-pyrazole-4-carbonitriles 4a–c, instead of 5-(5-amino-1-aryl-3-methyl-1H-pyrazole-4-yl)-1H-tetrazoles 5a–c as desired. In an attempt to obtain these tetrazole derivatives containing the methyl group at C3-position in the pyrazole ring, the amino group in 5-amino-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile 4c was protected by the reaction with sodium hydride and di-tert-butyl-dicarbonate (Boc). The tetrazole derivative 5c was synthesized from the protected compound 7c using analogue methodology to obtain 2a–c and 6a–c.     

Phosphorus–nitrogen compounds: Part 19. Syntheses,structural and electrochemical investigations,biological activities,and DNA interactions of new spirocyclic monoferrocenylcyclotriphosphazenes

The reactions of hexachlorocyclotriphosphazatriene, N₃P₃Cl₆, with N-alkyl-N-ferrocenylmethylethylene diamines, FcCH₂NH(CH₂)₂NHR₁ [R₁ = Me (1) and Et (2)], and sodium [3-(N-ferrocenylmethylamino)-1-propanoxide] (3) produce spirocyclic monoferrocenyl tetrachlorophosphazenes (1a–3a). The tetrapyrrolidinophosphazenes (1b–3b) are prepared from the reactions of corresponding phosphazenes (1a–3a) with excess pyrrolidine. The reaction of 1a with excess morpholine affords geminal-morpholino phosphazene (1c), whilst the reactions of 2a and 3a give diethylaminotrimorpholino (2c) and fully substituted morpholino products (3c), respectively. The structural investigations of the compounds are examined by Fourier transform IR, MS, ¹H, ¹³C, ³¹P NMR, DEPT, HETCOR, and HMBC techniques. The crystal structures of 3b and 3c are determined using X-ray crystallography. Cyclic voltammetric and chronoamperometric data show that compounds 1a–3a, 1b–3b, and 1c–3c exhibit electrochemically reversible one-electron oxidation of Fc redox centers which are hardly affected by the substituents on the phosphazene ring. The compounds 1b, 2b, 3b, and 3c are screened for antibacterial activities against Gram-positive and Gram-negative bacteria and for antifungal activities against yeast strains. In addition, the antituberculosis activities (in vitro) of these compounds are evaluated against INH-susceptible reference strain M. tuberculosis H37Rv, and six multi-drug resistant clinical M. tuberculosis isolates. Compound 2b is found to be the most active against the susceptible the reference strain. In addition, 1b, 2b, and 3c are active against all the multidrug-resistant clinical isolates at the highest concentrations. Gel electrophoresis data indicate that the compounds promote the formation of strand breaks in plasmid DNA. Almost all the concentrations lost of supercoiled DNA suggests that the compound 3b is very efficient plasmid-modifier. The compounds inhibit BamHI cleavage of pUC18 DNA while restricting HindIII.     

Transannular Anti-Michael Addition: Formation of 4H-Pyrazolo[5,1-c]thiazines

The reaction of 2-(diphenylmethylene)thietan-3-one (2) with 1,2,4,5-tetrazines (3a-c) in KOH/MeOH/THF gives 4H-pyrazolo[5,1-c]thiazines (7a-c). This novel condensation reaction proceeds via the intermediacy of an 8-(diphenylmethylene)-2H-1,4,5-thiadiazocin-7(8H)-one (5), which undergoes a multi-step rearrangement including a rare anti-Michael addition.     

Facile generation method for conjugated allenyl esters based on retro-Dieckmann-type ring-opening reactions

α-Alkynyl-α-ethoxycarbonyl cyclopentanones 1a-c and cyclohexanones 2a-c were readily synthesized by the reaction of ethyl 2-oxocyclopentanonecarboxylate 6 and ethyl 2-oxocyclohexanonecarboxylate 7 with alkynyllead triacetates 5a-c obtained from lithium acetylides 4a-c and lead tetraacetate. Treatment of 1a-c and 2a-c with 1 N KOH in THF or with n-Bu₄N⁺OEt⁻ in EtOH and THF gave the corresponding conjugated allenyl esters 8a-c, 9a-c, 10a-c, and 11a-c in good to excellent yields, respectively.     

Highly active ferrocenylamine-derived palladacycles for carbon–carbon cross-coupling reactions

{[(N-Methyl-N-p-R-benzyl)amino]benzyl}ferrocenes 4a–c (R = H(a), OCH₃(b), CH₃(c)) were synthesized by N-methylation of the corresponding sec-amines 3a–cwith the reagent CH₃I-t-BuOK. Treatment of 4a–c with Na₂PdCl₄ in the presence of NaOAc produced a pair of palladacycles σ-Pd[(η⁵-C₅H₅)Fe(η⁵- C₅H₃CH(C₆H₅)N(CH₃)CH₂-C₆H₄-R)]Cl(PPh₃) 5a–c (R = same as before) consisting of R_NR_P and S_NS_P configurations. The structure of 5a was determined by single crystal X-ray analysis. High catalytic activities of 5a–c for the Suzuki coupling of aryl chlorides with phenylboronic acid and the Heck reaction of bromobenzene with styrene were observed.     

A facile approach for the synthesis of novel substituted 4H-chromenes and condensation reactions of 4H-chromenes leading to chromenopyrrolones and triazolylchromenopyrrolones

A facile method has been developed for the synthesis of 4H-chromene-3-carboxylates 3a–d by the nucleophilic substitution reaction of 2-hydroxy-2H-chromene-3-carboxylates 2a–d with triethylsilane in the presence of BF₃·O(C₂H₅)₂. Cyclocondensation of 4H-chromene-3-carboxylates 3a–d with benzylamines 4a–d afforded a series of 2,3-dihydrochromenopyrrolones 5a–p and with propargylamine afforded 2-propynyl-2,3-dihydrochromenopyrrolones 6a–d. Click reaction of 6a–d with benzyl azides 7a–d provided a series of 1H-1,2,3-triazolylmethyl-2,3-dihydrochromenopyrrolones 8a–p. Thus synthesized compounds 3a–d, 5a–p, 6a–d, and 8a–p are novel heterocyclic compounds and being reported for the first time.     

Au(III)-catalyzed regio- and stereoselective tandem synthesis of oxazolo fused naphthyridines and isoquinolines from o-alkynylaldehydes

An efficient tandem approach for the regio- and stereoselective synthesis of oxazolo-fused naphthyridines 3a–g, 3i–l and isoquinolines 3h, 3m via the reaction of o-alkynylaldehydes 1a–i with chiral amino alcohols 2a–c under mild reaction conditions is described. The stereochemistry and structures of the products were assigned via NOESY and X-ray crystallographic studies.     

Rhodium(I) complexes with κP coordinated ω-phosphinofunctionalized alkyl phenyl sulfide, sulfoxide and sulfone ligands and their reactions with sodium bis(trimethylsilyl)amide and Ag[BF4]

Reactions of ω-diphenylphosphinofunctionalized alkyl phenyl sulfides Ph₂P(CH₂)_nSPh (n = 1, 1a; 2, 2a; 3, 3a), sulfoxides Ph₂P(CH₂)_nS(O)Ph (n = 1, 1b; 2, 2b; 3, 3b) and sulfones Ph₂P(CH₂)_nS(O)₂Ph (n = 1, 1c; 2, 2c; 3, 3c) with dinuclear chlorido bridged rhodium(I) complexes [(RhL₂)₂(μ-Cl)₂] (L₂ = cycloocta-1.5-diene, cod, 4; bis(diphenylphosphino)ethane, dppe, 5) afforded mononuclear Rh(I) complexes of the type [RhCl{Ph₂P(CH₂)_nS(O)_xPh-κP}(cod)]¹ (n/x = 1/0, 6a; 1/1, 6b; 1/2, 6c; 2/0, 8a; 2/1, 8b; 2/2, 8c; 3/0, 10a; 3/1, 10b; 3/2, 10c) and [RhCl{Ph₂P(CH₂)_nS(O)_xPh-κP}(dppe)] (n/x = 1/0, 7a; 1/1, 7b; 1/2, 7c; 2/0, 9a; 2/1, 9b; 2/2, 9c; 3/0, 11a; 3/1, 11b; 3/2, 11c) having the P^S(O)_x ligands κP coordinated. Addition of Ag[BF₄] to complexes 6-11 in CH₂Cl₂ led with precipitation of AgCl to cationic rhodium complexes of the type [Rh{Ph₂P(CH₂)_nS(O)_xPh-κP,κS/O}L₂][BF₄] having bound the P^S(O)_x ligands bidentately in a κP,κS (13a-18a, 15b-18b) or a κP,κO (13b, 14b, 13c-18c) coordination mode. Unexpectedly, the addition of Ag[BF₄] to 6a in THF afforded the trinuclear cationic rhodium(I) complex [Rh₃(μ-Cl)(μ-Ph₂PCH₂SPh-κP:κS)₄][BF₄]₂·4THF (12·4THF) with a four-membered Rh₃Cl ring as basic framework. Addition of sodium bis(trimethylsilyl)amide to complexes 6-11 led to a selective deprotonation of the carbon atom neighbored to the S(O)_x group (α-C) yielding three different types of organorhodium complexes: a) Organorhodium intramolecular coordination compounds of the type [Rh{CH{S(O)_xPh}CH₂CH₂PPh₂-κC,κP}L₂] (22a-c, 23a-c), b) zwitterionic complexes [Rh{Ph₂PCHS(O)_xPh-κP,κS/O}L₂] having κP,κS (21a, 21b) and κP,κO (20b/c, 21c) coordinated anionic [Ph₂PCHS(O)_xPh] ligands, and c) the dinuclear rhodium(I) complex [{Rh{μ-CH(SPh)PPh₂-κC:κP}(cod)}₂] (19). All complexes were fully characterized spectroscopically and complexes 15b, 15c, 12·4THF and 19·THF additionally by X-ray diffraction analysis. DFT calculations of zwitterionic complexes gave insight into the coordination mode of the [Ph₂PCHS(O)Ph] ligand (κP,κS versus κP,κO).     

Conjugated C3 symmetric aryl tripyrroles and aryl bipyrroles: synthesis,optical and electronic properties

Conjugated C₃ symmetric molecules have been pursued for their fluorescent and electrochemical properties. The synthesis of conjugated C₃ symmetric aryl tripyrroles has been performed by a route featuring three steps from trimethyl 1,3,5-benzene tricarboxylate 6: copper-catalyzed cascade addition of vinylmagnesium bromide to convert the carboxylates into γ,δ-unsaturated ketones, Tsuji–Wacker olefin oxidations to form tris(1,4-dione) 9, and Paal–Knorr condensation with ammonia and different amines to furnish the final tripyrroles (30–60% yields). In addition, incomplete reaction of vinylmagnesium bromide to 6 provided benzoate 8 possessing two γ,δ-unsaturated ketones, which were similarly converted to 3,5-dipyrrolylbenzoates 11. The absolute fluorescence quantum yields (Φ_fl) and electrochemical properties of 5a–c and 11a–c were investigated. The Φ_fl are the first reported for such compounds and they ranged between 2 and 40%, contingent on structure and solvent polarity. Cyclic voltammetry revealed that the compounds could be both oxidized and reduced, albeit irreversibly. The oxidation potentials (E_ox) varied between 0.73 V and 1.2 V and the reduction potentials (E_red) varied from −0.83 V to −1.36 V. The lowest redox processes were measured for the NH–pyrrole 5a. Moreover, tripyrrole 5a was air stable and on oxidative doping with ferric chloride exhibited a 50 nm bathochromic shift in its absorbance spectrum.     

Studies on the Suzuki reaction on methyl 1-(2-bromoaryl)-5-oxo-3-aryl/heteroaryl-pyrrolidin-2-carboxylate derivatives: synthesis of N-aryl modified monocyclic γ-lactam derivatives in search for newer antibacterial agents

A large number of novel N-aryl modified monocyclic γ-lactam derivatives have been prepared via Pd(0) catalyzed heteroarylation in the N-aryl part of (±) cis and (±) trans γ-lactam carboxylate derivatives 3(a–f) and 6(a–f), respectively, with furan-2-boronic acid and thiophen-2-boronic acid. (±) cis Methyl 1-(2-bromoaryl)-5-oxo-3-aryl/heteroarylpyrrolidin-2-carboxylate derivatives 3(a–f), were prepared in good yields from 1(a–f) via hydrolysis, stereoselective decarboxylation, followed by esterification. Corresponding trans isomers 6(a–f) were prepared by the standard method already reported by us.     

A novel and easy two-step,microwave-assisted method for the synthesis of halophenyl pyrrolo[2,3-b]quinoxalines via their pyrrolo precursors. Evaluation of their bioactivity

A novel, two-step, facile route for the synthesis of pyrrolo[2,3-b]quinoxalines via 2,3-dioxopyrroles, enhanced by microwave irradiation, is presented. The newly synthesized 2,3-dioxo-5-halophenyl pyrrolo precursors 4a–c as well as the non-aromatized ethyl 2-(4-halophenyl)-1-methyl-2,4-dihydro-1H-pyrrolo[2,3-b]quinoxaline-3-carboxylates 6a–c and the aromatized ethyl 2-(4-halophenyl)-1-methyl-1H-pyrrolo[2,3-b]quinoxaline-3-carboxylates 7a–c were evaluated for their antioxidant, cytostatic, and antiviral properties. Most of them proved to be potent hydroxyl radical scavengers and inhibited in vitro lipid peroxidation. The compounds showed moderate antiproliferative activity, while 6a inhibited vaccinia virus at an EC₅₀ value of 2 μM, and 4c and 6c inhibited Sindbis virus at EC₅₀ values of 4 μM.     

Rapid syntheses of (±)-pterocarpans and isoflavones via the gold-catalyzed annulation of aldehydes and alkynes

(±)-Pterocarpan and analogues (4a-c) have been synthesized efficiently via the annulation of salicylaldehydes (1a, 1b and 1c) and o-methoxymethoxylphenylacetylene (2a), followed by a one-pot reduction and acidic cyclization of the ketones (3a-c). In addition, isoflavone derivatives (5a-c) have been synthesized rapidly, in two steps, via the annulation of salicylaldehyde (1a) and arylacetylenes (2b, 2c and 2d), followed by IBX/DMSO oxidation of the isoflavanones (3d, 3e and 3f).     

Columnar catenar bisoxazoles and bisthiazoles

Three new series of catenar liquid crystals 1a–c derived from heterocyclic bisoxazoles and bisthiazoles exhibiting columnar phases were reported. All compounds 1a–c exhibited hexagonal columnar phases, which were confirmed by powder XRD diffractometer. Compounds 1a have a slightly wider temperature range of columnar phases than that of compounds 1b, which might be attributed to higher dipole polarized in 1a. A N_cell and R_ar value equal to 2.54–2.76 and 19.99–20.45 Å² within a slice of 9.0 Å thick were obtained for three derivatives 1a–c (all ns=12), indicating that a single molecule was packed within columns in Col_h phases. All derivatives showed good stabilities at temperature below T=408 °C on TGA. The PL spectra of all compounds 1a–c showed one intense peak at λ_max=505–510 nm, and these photoluminescent emissions originated from quinoxaline moiety.     

Stereoselective tandem synthesis of oxazolo-fused pyrroloquinolines from o-alkynylaldehydes via Ag(I)-catalyzed regioselective 5-exo-dig ring closure

A tandem approach for the regio- and stereoselective synthesis of oxazolo-fused pyrroloquinolines 3a–l via the reaction of o-alkynylaldehydes 1a–i with chiral amino alcohols 2a–c under mild reaction conditions is described. The possible participation of the pyridine ring in the regioselective formation of 5-exo-dig cyclized products was supported by the controlled experiments. The structures and stereochemistry of the products were confirmed by NOESY and X-ray crystallographic studies.     

Synthesis,photophysical and nonlinear optical properties of microwave synthesized 4-tetra and octa-substituted lead phthalocyanines

This work presents the photophysical and nonlinear optical behaviour of newly synthesized complexes: 2,(3)-tetrakis(4-benzyloxyphenoxyphthalocyaninato) lead (5a) and 2,3-octakis(4-benzyloxyphenoxyphthalocyaninato) lead (6a). The nonlinear optical behaviour of complexes 5a and 6a are compared with those of 2,(3)-tetraphenoxyphthalocyaninato lead (5b), 2,(3)-tetrakis(4-t-butylphenoxyphthalocyaninato) lead (5c), 2,3-octaphenoxyphthalocyaninato lead (6b) and 2,3-octakis(4-t-butylphenoxyphthalocyaninato) lead (6c). The synthesis of 5a and 6a was performed using microwave irradiation. Photophysical properties were studied for these complexes in dimethylsulfoxide, dimethylformamide, toluene, tetrahydrofuran and chloroform. The fluorescence spectra were different from excitation spectra due to demetallation upon excitation. High triplet quantum yields ranging from 0.80 to 0.86 (in DMSO, DMF and toluene) and low triplet lifetimes (20–50 μs in DMSO, and <10 μs in the rest of the solvents) were observed due to the presence of heavy atom. Nonlinear optical properties were studied in dimethylsulfoxide. The optical limiting threshold intensity (I_lim) for the PbPc derivatives were calculated and ranged from 2.1 to 6.6 W/cm².     

A new Fe fluorescent chemosensor based on aggregation-induced emission

A new tetraphenylethylene (TPE)-based sensor M1 bearing double 2-methylpyridyl-2-methylthiophenylamino units linked with triazole moieties was reported. Both UV–vis and fluorescence spectroscopic studies demonstrated that M1 was highly sensitive and selective toward Fe³⁺ over other metal ions in THF/H₂O solution based on the aggregation-induced emission quenching mechanism. The lowest detection limit of M1 for Fe³⁺ is 0.7 μM. The detailed fluorescent titration study suggested that the binding stoichiometry of the M1–Fe³⁺ complex was 1:2, and the structure between M1 and the Fe³⁺ complex was confirmed by the ¹H NMR titration.     

Microwave-assisted synthesis of novel bis(2-thioxothiazolidin-4-one) derivatives as potential GSK-3 inhibitors

(5Z,5′Z)-3,3′-(1,4-Phenylenebis(methylene)-bis-(5-arylidene-2-thioxothiazolidin-4-one) derivatives (5a-r) have been synthesized by the condensation reaction of 3,3′-(1,4- or 1,3-phenylenebis(methylene))bis(2-thioxothiazolidin-4-ones) (3a,b) with suitably substituted aldehydes (4a-f) or 2-(1H-indol-3-yl)2-oxoacetaldehydes (8a-c) under microwave conditions. The bis(2-thioxothiazolidin-4-ones) were prepared from the corresponding primary alkyl amines (1a,b) and di-(carboxymethyl)-trithiocarbonyl (2). The 2-(1H-indol-3-yl)-2-oxoacetaldehydes (8a-c) were synthesized from the corresponding acid chlorides (7a-c) using HSnBu₃.