Copper(I)-Catalyzed Synthesis of 1,4-Disubstituted 1,2,3-Triazoles from Azidoformates and Aryl Terminal Alkynes.

The copper(I)-catalyzed azide-alkyne cycloaddition reaction has been extensively studied and widely applied in organic synthesis. However, the formation of 1,2,3-triazoles with electron-deficient azide has been a challenging problem. In this report, we have demonstrated the formation of regioselective 1,4-disubstituted 1,2,3-triazoles from various types of aryl terminal alkynes and azidoformates, which are electron-deficient azides, using a commercialized [Cu(CH3CN)4]PF6 copper(I) catalyst under mild conditions.

Effects of a novel carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside on pleiotropic induction of cell death in prostate cancer cells with different androgen responsiveness.

Prostate cancer is the most frequently diagnosed cancer and is one of the leading causes of male cancer death in the world. Recently, in the course of our screening for a novel anticancer compound, we synthesized carbocyclic analogs of pyrrolo[2,3-d]pyrimidine nucleoside; compounds 5, and 6. In the current study, we report the effects of compound 5 on pleiotropic induction of cell death via up-regulation of AR-associated p21(Cip1) protein in prostate cancer cells with different androgen responsiveness, such as LNCaP (androgen-dependent and -sensitive), LNCaP(C4-2) (androgen-independent and -sensitive; androgen-refractory), and DU145 (androgen-independent and -insensitive) cells. The treatment of LNCaP cells with 6 µM compound 5 for 24 h stimulated the androgen receptor (AR) activity and dramatically up-regulated transcription (56-fold) of p21(Cip1), which, in turn, induces typical apoptosis in the cells. However, induction of apoptosis through up-regulation (23-fold) of AR-associated p21(Cip1) achieved in LNCaP(C4-2) cells was possible by intensive cell treatment with compound 5 (9 µM, 48 h), because the cells are less sensitive and independent to androgen than LNCaP cells. Furthermore, 6 µM compound 5-treated DU145 cells, which exhibit extremely low AR activation due to no androgen responsiveness and dependency, showed neither up-regulation of p21(Cip1) nor apoptotic induction. Instead, a different type of cell death, autophagy-like death through the LC3B-associated autophagosome formation, was obviously induced in DU145 cells. Taken together, our results suggest that pleiotropic induction of prostate cancer cell death by compound 5 is determined by how efficiently and how abundantly androgen-dependent activation of the AR occurs, whereas compound 6 shows no induction of apoptosis in LNCaP cells.

Palladium-catalyzed benzylation of arylboronic acids with N,N-ditosylbenzylamines.

The palladium-catalyzed coupling of N,N-ditosylbenzylamines with arylboronic acids has been investigated, and the resulting diarylmethanes were obtained in high yields. Conversion of the amine to a N,N-ditosylimide group provided an efficient leaving group for the Pd-catalyzed benzylation of arylboronic acids.

Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques.

Fluorescence probes that can detect Aß (ß-amyloid peptide) plaque are important tools for diagnosis of Alzheimer's disease (AD), and 4-N-methylamino-4'-hydroxystilbene (SB-13) is one of the promising candidate molecules. We report here the synthesis of SB-13 derivatives that consist of various electron donating/withdrawing moieties and distinct size of N-substituents. The synthesized compounds were screened for detection of Aß40 fibrils in vitro. Four compounds exhibited more than sixfold intensity increase, and they were further analyzed for detail bindings and Aß plaque imaging. Among these molecules, compound 42 meets two critical requirements for imaging agent; high fluorescence responsiveness and strong binding affinity. This compound showed more than 25-fold increase with the dissociation constant of 1.13±0.37µM. In AD mouse brain tissue, 42 selectively stained Aß plaque, more specifically peripheral regions of Aß plaque. This finding demonstrated its potential use as brain-imaging agents for AD studies.

Synthesis and characterization of carboxylated PBAMO copolymers as promising prepolymers for energetic binders.

The carboxylated poly[3,3-bis(3-azidomethyl)oxetane] (PBAMO) copolymers (poly(BAMO-carboxylate)) were synthesized by substitution of poly[3,3-bis(3-chloromethyl)oxetane] (PBCMO) with potassium carboxylate and sodium azide in DMSO. The synthesized compounds were characterized using various analytical techniques, such as Fourier-transform infrared (FT-IR) spectroscopy, inverse-gated decoupling 13C-nuclear magnetic resonance (13C NMR) spectroscopy, gel permeation chromatography (GPC), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), calorimetry, friction, and impact sensitivity analysis. These poly(BAMO-carboxylate) compounds have better thermal properties, with lower glass transition temperatures (ranging from -43 °C to -51 °C) than PBAMO (-37 °C) and higher thermal decomposition temperatures (233-237 °C) than PBAMO (211 °C). Moreover, poly(BAMO0.80-octanoate0.20) and poly(BAMO0.78-decanoate0.22) have higher heats of combustion (5226 and 5665 kJ mol-1, respectively) and negative formation enthalpies (-0.17 and -0.55 kJ g-1, respectively), while PBAMO has lower heat of combustion (3125 kJ mol-1) and positive formation enthalpy (0.06 kJ g-1). The poly(BAMO-carboxylate) compounds have higher values (38-50 J) than that of PBAMO (14 J) in the impact sensitivities. This is a valuable study for improving the properties of PBAMO, which is a high energetic polymeric binder but difficult to handle because of its sensitivity. Therefore, poly(BAMO-carboxylate) could be a good candidate as a prepolymer for designing the energetic polymeric binder.

Azide-alkyne cycloaddition reactions in water via recyclable heterogeneous Cu catalysts: reverse phase silica gel and thermoresponsive hydrogels.

Functionalized reverse phase silica gel and thermoresponsive hydrogels were synthesized as heterogeneous catalysts supports. Cu(i) and Cu(ii) catalysts immobilized onto two types of supports were prepared and characterized. The copper catalyzed azide-alkyne cycloaddition was performed in water via a one-pot reaction and yielded good results. These catalysts are air stable and reusable over multiple uses.

Ecofriendly synthesis and characterization of carboxylated GAP copolymers.

Carboxylated GAP copolymers (polyGA-carboxylate) compounds (1-7), were synthesized by the simultaneous substitution reaction with PECH, sodium azide, and sodium carboxylate in DMSO. The synthesized compounds (1-7) were characterized by various analysis tools, such as Fourier transform infrared (FT-IR), inverse gated decoupling 13C-nuclear magnetic resonance (13C NMR), gel permeation chromatography (GPC), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), calorimetry, and friction and impact sensitivity. These poly(GA-carboxylate) compounds (1-7) have better thermal properties owing to their lower glass transition temperatures, from -48 °C to -55 °C, compared to glycidyl azide polymer (GAP) (-49 °C) and similar first thermal decomposition temperatures (228-230 °C) in comparison to GAP (227 °C), regardless of the introduction of the carboxylate group in GAP. Moreover, poly(GA0.8-butyrate0.2) and poly(GA0.8-decanoate0.2) have higher heats of combustion (2331 and 2976 kJ mol-1) and negative formation enthalpies (-0.75 and -2.02 kJ g-1), while GAP has a lower heat of combustion (2029 kJ mol-1) and positive formation enthalpy (1.33 kJ g-1). Therefore, poly(GA-carboxylate) could be a good candidate for the polymeric binder in solid propellants.

Synthesis and evaluation of cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[(124)I]iodouracil: a new potential PET imaging agent for HSV1-tk expression.

In our pursuit to find an appropriate reporter probe for herpes simplex virus type-1 thymidine kinase (HSV1-tk), a carbocyclic nucleoside analogue, cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[124I]iodouracil, has been efficiently synthesized. A Pd(0)-catalyzed coupling reaction together with organotin and exchange reactions for radiolabeling gave more than 80% radiochemical yield with greater than 95% radiochemical purity and 1.15 GBq/mumol specific activity. Biological data reveal that the analogue is stable in vitro, less toxic than ganciclovir (GCV), and selective to HSV1-tk-expressed cells based on micro positron emission tomography (microPET) image analyses. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5-iodouridine (carbocyclic d4IU) is a potential imaging probe for HSV1-tk.

Hydrogenation and dehalogenation under aqueous conditions with an amphiphilic-polymer-supported nanopalladium catalyst.

An amphiphilic polystyrene-poly(ethylene glycol) resin supported nanopalladium particle catalyzed hydrogenation of olefins and hydrodechlorination of chloroarenes under aqueous conditions is presented.

Synthesis and Characterization of [Mn(III)(6)(N-formylsalicylhydrazidate)(6)(MeOH)(6)]: A New Type of Macrocyclic Hexanuclear Manganese Cluster.

The macrocyclic hexanuclear metal cluster, [Mn(III)(6)(fshz)(6)S(6)], 1 (S = MeOH), was prepared using a trianionic pentadentate ligand, N-formylsalicylhydrazidate (fshz(3)(-)). Due to the meridional coordination of the ligand to the metal ion, the ligand is not only bridging the ring metal ions using a hydrazide N-N group but also enforcing the stereochemistry of the metal ions as a propeller configuration. The alternations of the chiralities of the metal centers expand the cyclic ring system of complex 1 to the 24-membered ring system. The neutral hexanuclear manganese complex with noncrystallographic pseudo-C(3)(i)() symmetry is in the crystallographic inversion center. The disc-shaped hexanuclear cluster is 1.8 nm in diameter and 0.8 nm in thickness and has a vacant cavity in the center of the cluster. Three solvent molecules coordinated at the metal centers with Lambda configuration are in one face of the cluster, and the remaining three solvent molecules coordinated at the other metal centers with Delta configuration are in the other face of the cluster. The two faces of the cluster have opposite chiralities to each other. The crystal packing structure of complex 1 shows that the disc-shaped hexanuclear clusters are aligned approximately along the crystallographic a axis. The cavities of the clusters in the crystal structure are also aligned, and one-dimensional channels are formed. The solution integrity of the cluster was addressed using solution mass spectrometry, paramagnetically shifted (1)H NMR spectroscopy, and UV-visible spectroscopy. Crystallographic data for 1: triclinic, P&onemacr;, a = 10.0237(9) Å, b = 15.096(1) Å, c = 15.617(1) Å, alpha = 112.142(5) degrees, beta = 106.615(5) degrees, gamma = 99.958(7) degrees, V = 1989.8(3) Å(3), Z = 2, D(calcd) = 1.510 g cm(-)(1), R1 = 0.0502 and wR2 = 0.1424 for 4249 reflections with I > 2sigma(I), GOF = 1.065.

A facile synthesis of cis-4-amino-2-cyclopentene-1-methanol, a key intermediate for the synthesis of carbocyclic nucleosides.

A number of carbocyclic nucleosides can be synthesized from (+/-)-cis-4-amino-2-cyclopentene-1-methanol (3). Carbocyclic amino alcohol 3 is a key intermediate that makes possible the efficient synthesis of the carbocyclic nucleosides. In this study we wish to report an efficient synthesis of carbocyclic amino alcohol 3 from inexpensive and readily available starting material. The synthetic route employed cyclopentadiene (4) as a starting material and proceeded in 38% overall yield through 6 steps involving a hetero Diels-Alder reaction and an aza-Claisen rearrangement.

Synthesis of carbocyclic 1-[4-(hydroxymethyl)cyclopent-2-enyl]-1,2,4-triazole-3-carboxamide and its derivatives.

The synthesis of carbocyclic 1-[4-(hydroxymethyl)cyclopent-2-enyl]-1,2,4-triazole-3-carboxamide (6a) and its derivatives was achieved from triol 10 in excellent overall yield. This route involves a Pd(0)-catalyzed coupling reaction as a key step.

One-pot reductive mono-N-alkylation of aniline and nitroarene derivatives using aldehydes.

One-pot reductive mono-N-alkylation of aniline and nitroarene derivatives using various aldehydes by Pd/C catalyst in aqueous 2-propanol solvent with ammonium formate as in situ hydrogen donor is illustrated. The reaction proceeded smoothly and selectively with excellent yield at room temperature. Our protocol presents a facile, economical, and environmentally benign alternative for reductive amination.

Face-driven corner-linked octahedral nanocages: M6L8 cages formed by C3-symmetric triangular facial ligands linked via C4-symmetric square tetratopic Pd(II) ions at truncated octahedron corners.

The face-driven corner-linked truncated octahedral nanocages, [Pd6L8]12+ (1, L1 = N,N',N' '-tris(3-pyridinyl)-1,3,5-benzenetricarboxamide; 2, L2 = N,N',N' '-tris(4-pyridinylmethyl)-1,3,5-benzenetricarboxamide), were prepared with eight C3-symmetric tridentate ligands and six square planar tetratopic palladium(II) ions. The combination of the nitrogen donor atom at a approximately 120 degrees kink position of the carboxamido pyridinyl group and the tilted pyridyl versus the facial plane of the ligands can provide the needed curvature for the formation of octahedral cages. The nitrogen atoms can coordinate to the square planar palladium(II) ions to form kinks with approximately 120 degrees angles at the C4-symmetric square planar corners of the truncated octahedron. Depending on the conformation of the ligand, L1, two different truncated octahedral cages of around 2.4 nm in diameters were formed. The major form of 1 with syn-conformational ligands has a cavity volume of approximately 1600 A3. The cage has 12 ports (3.4 x 3.5 A2) at all edges of the octahedron. The minor form of cage 1 with anti-conformational ligands has a slightly increased cavity volume ( approximately 1900 A3) and port size (3.3 x 8.0 A2). The insertion of a methylene group in L2 has not only increased the cavity volume of 2 to approximately 2200 A3 but also enlarged the port size to 4.1 x 8.0 A2. However, an atomic force microscopy (AFM) study of cage 2 showed that the cages had a height of 1.8 +/- 0.1 nm. This value is about 30% smaller than the calculated size of 2.6 nm from the crystal structure. This tip-induced decrease in height in cage 2 suggests the nonrigidity of cage 2.