Synthesis of 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carbonitriles and -6-carboxylic acid esters

Dieckmann ring closure reactions of 4-[(2-cyanoethyl)substituted amino]-2-phenyl-5-pyrimidinecarboxylates (Ha-f) afforded several 5,6,7,8-tetrahydro-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitriles (IIIa-f). The open-chain intermediates (IIa-f) were prepared by dechloroamination of 5-carbethoxy-4-chloro-2-phenylpyrimidine (1a) with several 3-substituted amino- propionitriles. Alkylation of the sodium salt of 5,6,7,8-tetrahydro-8-methyl-5-oxo-2-phenyl-pyrido[2,3-d]pyrimidine-6- carbonitrile (IIIa) with methyl iodide in DMF resulted in methylation at C-6 to afford IV. Tosylation of IIIa in pyridine gave the corresponding tosyl ester (V) of the enolic form. Oxidative dehydrogenation at the 6,7-position resulted when IIIa reacted with thionyl chloride, affording 5,8-dihydro-8-methyl-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitrile (VII). Dechloroamination of la or 5-carbethoxy-4-chloro-2-methylthiopyrimidine (Ib) with ethyl 3-ethylaminopropionate followed by Dieckmann cyclization of the resulting open-chain intermediates gave the corresponding ethyl 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylates IX'a and IX'b, respectively. These exist predominately in the enol form and undergo alkylation and oxidation reactions similar to IIIa.     

Thieno[2,3-d]pyrimidines. I. A new method for the preparation of esters and amides of thieno[2,3-d] pyrimidine-6-carboxylic acids

A novel method for the preparation of esters and amides of thieno[2,3-d]pyrimidine-6-carb-oxylic acids was described. A typical example was the direct formation of ethyl 5-amino-2-methylthiothieno[2,3-d]pyrimidine-6-earboxylate(IIIa) from 4-chloro-2-methylthio-5-pyrimidine-carbonitrile (Ia) and ethyl mercaptoacetate in refluxing ethanol containing sodium carbonate. Displacement of the methylthio group in IIIa by various amines gave the corresponding amino derivatives. The reactions of IIIa and related compounds with acetylating agents such as acetic anhydride or chloroacetyl chloride gave various products. Treatment of 5-carbethoxy-4-chloro-2-phenylpyrimidine(IV) with methyl mercaptoacetate afforded the dechloro intermediate diester Va, which cyclized on reaction with sodium ethoxide to form methyl 5-hydroxy-2-phenylthieno-[2,3-d]pyrimidine-6-carboxylate (Vla). The synthesis was expanded to include the preparation of various new 2,4,5-trisubstituted thieno[2,3-d]pyrimidine-6-carboxylic acid esters and amides (Charts I-V).     

Development of a peptide inhibitor-based cantilever sensor assay for cyclic adenosine monophosphate-dependent protein kinase

A highly sensitive nanomechanical cantilever sensor assay based on an electrical measurement has been developed for detecting activated cyclic adenosine monophosphate (cyclic AMP)-dependent protein kinase (PKA). Employing a peptide derived from the heat-stable protein kinase inhibitor (PKI), a magnetic bead system was first selected as a vehicle to immobilize the PKI-(5-24) peptide for capturing PKA catalytic subunit and the activity assay was applied for indirectly assessing the binding. Synergistic interactions of adenosine triphosphate (ATP) and the peptide inhibitor with the kinase were then investigated by a solution phase capillary electrophoretic assay, and by surface plasmon resonance technology which involved immobilization of the peptide inhibitor. After systemically evaluated by a homogeneous direct binding assay, the ATP-dependent recognition of the catalytic subunit of PKA by PKI-(5-24) was successfully transferred on to the nanomechanical cantilevers at protein concentrations of 6.6 pM-66 nM, exhibiting much higher sensitivity and wider dynamic range than the conventional activity assay. Thus, direct assessment of activated kinases using the cantilever sensor system functionalized with specific peptide inhibitors holds great promise in analytical applications and clinical medicine.     

Uncommon ferromagnetic interactions in a homometallic Co(II) chain bridged by a single end-to-end azide

A new one-dimensional heterochiral coordination polymer [Co(bmdt)(N3)2].MeCN (1.MeCN) with well-isolated chains was prepared via a self-assembly process. Magnetic data show that intrachain ferromagnetic couplings via the single end-to-end azide group are observed, which is an extraordinary case among the azide-bridged Co(II) systems.     

Sensitized near-IR luminescence of Ln(III) complexes with benzothiazole derivatives

Lanthanide complexes with benzothiazole derivatives (Btz-R, R = OCH(3) and OH) and terpyridine (tpy) ligands were synthesized, and their photophysical properties were precisely investigated. The free Btz-OCH(3) ligand in toluene, excited with UV light, produced the normal emission bands around 410 nm, whereas Btz-OH produced a strong excited-state intramolecular proton transfer (ESIPT) band at 510 nm. The Ln(III) complexes (Ln = Nd, Er, and Yb) exhibited sensitized near-IR luminescence when the Btz-R ligands were excited. The sensitized luminescence quantum yields (Phi(Ln)) of the lanthanide complexes were markedly enhanced by ESIPT: for [Nd(Btz-R)(tpy)] in toluene solution, Phi(Ln) = 0.04% for Btz-OCH(3) and 0.39% for Btz-OH. The sensitized luminescence of the Er(III) complexes (Phi(Ln) = 0.002% for Btz-OCH(3) and 0.009% for Btz-OH) was less efficient than that of the Nd(III) complexes. This difference is due to the smaller energy gap between the emitting and ground levels of the Er(III) ion. The rate constants for the energy transfer from Btz-R to Ln(III) were about approximately 10(9) s(-1), as evaluated by the F?rster resonance energy transfer mechanism.     

Continuous countercurrent extraction of hemicellulose from pretreated wood residues

Two-stage dilute acid pretreatment followed by enzymatic cellulose hydrolysisis an effectivemethod for obtaining high sugar yields from wood residuessuchassoftwood forest thinnings. In the first-stage hydrolysis step, most of the hemicellulose is solubilized using relatively mild conditions. The soluble hemicellu losic sugars are recovered from the hydrolysateslurry by washing with water. The washed solids are then subjected tomoresevere hydrolysis conditions to hydrolyze approx 50% of the cellulose to glucose. The remaining cellulose can further be hydrolyzed with cellulase enzyme. Our process simulation indicates that the amount of water used in the hemicellulose recovery step has a significan tim pact on the cost of ethanol production. It is important to keep water usage as low as possible while mainta ining relatively high recovery of solublesugars. To achieve this objective, a prototype pilot-scale continuous countercurrent screw extractor was evaluated for the recovery of hemicellulose from pretreated forest thinnings. Using the 274-cm (9-ft) long extractor, solubles recoveries of 98, 91, and 77% were obtained with liquid-to-insoluble solids (L/1S) ratios of 5.6, 3.4, and 2.1, respectively. An empirical equation was developed to predict the performance of the screwextractor. This equation predicts that soluble sugar recovery above 95% can be obtained with an L/IS ratio as low as 3.0.     

Electro-optic applications of soluble polypyrrole

The optical transmittance of the film spin-cast from the polypyrrole(PPy) solution in chloroform depended on the thickness of the film. The film with 80% transmittance showed a surface resistivity of 23kΩ/□. A TN-LCD cell with rubbed PPy films as the LC alignment layers responded properly to an applied potential of 3.0V. Reflective mode cholesteric LCD cells made with black PPy film electrodes responded to AC fields to switch between the planar and focal conic states. PPy with imine structures introduced by deprotonation of doped PPy with NaOH solution was used as a diode material to exhibit a photo-current on exposing to light.     

Study on a separation method of radionuclides (Ba, Sr) from LiCl salt wastes generated from the electroreduction process of spent nuclear fuel

In this paper, a separation method of radionuclides (Ba, Sr) from LiCl salt wastes generated from the electroreduction process of spent nuclear fuel was studied to recover pure LiCl salts and reduce radioactive wastes. The method consisted of chemical conversion process of BaCl₂ and SrCl₂ in LiCl molten salts by using lithium compounds and vacuum distillation process of LiCl salts. In the chemical conversion, BaCl₂ and SrCl₂ in LiCl molten salts were mainly converted into (Ba,Sr)CO₃ or (Ba,Sr)SO₄. Contents of Ba and Sr in LiCl salts recovered from the vacuum distillation process were equal to about 0.01 of initial concentrations of Ba and Sr in LiCl molten salts. These results will be utilized to recycle the LiCl salt wastes.