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New reaction products, useful as additives for functional fluids, are obtained by reacting, at elevated temperature, (A) a triazole having the formula IA or IB: STR1 wherein R7 is hydrogen or a C1 -C20 alkyl residue; R8 and R9 are the same or different and each is C1 -C20 alkyl, C3 -C20 alkenyl, C5 -C12 cycloalkyl, C7 -C13 aralkyl, C6 -C10 aryl or R8 and R9, together with the nitrogen atom to which they are attached, form a 5-, 6- or 7-membered heterocyclic residue or R8 and R9 is each a residue of formula: wherein X is O, S or N(R12), R12 is hydrogen or C1 -C20 alkyl, “alkylene” is a C1 -C12 alkylene residue and n is 0 or an integer from 1 to 6; R10 is hydrogen, C1 -C20 alkyl or C6 -C10 aryl or C7 -C18 alkyl phenyl; and R11 is hydrogen, C1 -C20 alkyl or a residue –CH2 NR8 R9 wherein R8 and R9 have their previous significance; with (B) an organodithiophosphate having the formula: STR2 in which R13 is a C1 -C20 alkyl or C7 -C18 alkyl phenyl or C7 -C13 aralkyl group, M is a metal ion of Group IA, IB, IIA, IIB, VB, VIB, VIIB or VIII of the Periodic System of Elements, and y is the valency of M.

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Mild palladium-catalyzed aminations of aryl tosylates and the first aminations of heteroaryl tosylates are described. In the presence of the combination of L2Pd(0) (L = P(o-tol)3) and the hindered Josiphos ligand CyPF-t-Bu, a variety of primary alkylamines and arylamines react with both aryl and heteroaryl tosylates at room temperature to form the corresponding secondary arylamines in high yields with complete selectivity for the monoarylamine. These reactions at room temperature occur in many cases with catalyst loadings of 0.1 mol % and 0.01 mol % in one case, constituting the most efficient aminations of aryl tosylates by nearly 2 orders of magnitude. This catalyst is made practical by the development of a convenient method to synthesize the L2Pd(0) precursor. This complex is stable to air as a solid. In contrast to conventional relative rates for reactions of aryl sulfonates, the reactions of aryl tosylates are faster than parallel reactions of aryl triflates, and the reactions of aryl tosylates are faster than parallel or competitive reactions of aryl chlorides. Copyright

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To improve definition of the physical and hormonal support of bone formation, we studied differentiation of human osteoblasts in vitro at varying combinations of ACTH, 1alpha,25-dihydroxyvitamin D 3 (1,25(OH) 2 D), and extracellular calcium, with and without added cortisol. Bone mineralization, alkaline phosphatase activity, and osteoblast-specific markers RunX2, osterix, and collagen I increased with 10 pM ACTH, 10 nM 1,25(OH) 2 D, or at 2 mM calcium with important synergistic activity of combinations of any of these stimuli. Signals induced by ACTH at 10-30 min included cAMP, TGF-beta, and Erk1/2 phosphorylation. Affymetrix gene expression analysis showed that 2 h treatment of ACTH or 1,25(OH) 2 D increased the expression of bone regulating and structural mRNAs, including collagen I, biglycan, the vitamin D receptor, and TGF-beta. Accelerating expression of these bone-specific genes was confirmed by quantitative PCR. Expression of 1,25(OH) 2 D 1alpha-hydroxylase (1alpha-hydroxylase) increased with 1,25(OH) 2 D, ACTH, and extracellular calcium from 0.5 to 2 mM. Unlike renal 1alpha-hydroxylase, in osteoblasts, 1alpha-hydroxylase activity is independent of parathyroid hormone. In keeping with calcium responsivity, calcium-sensing receptor RNA and protein increased with 10 nM ACTH or 1,25(OH) 2 D. Inclusion of 200 nM cortisol or 10 nM ACTH in differentiation media blunted osteoblasts alkaline phosphatase response to 1,25(OH) 2 D and calcium. Our results point to the importance of ACTH in bone maintenance and that extra skeletal (renal) 1,25(OH) 2 D is required for bone mineralization despite 1alpha-hydroxylase expression by osteoblasts.

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The reaction of N,N’-di-tert-butylethylenediamine with glyoxal in water gives initially trans-2,3-dihydroxy-1,4-di-tert-butylpiperazine, 6f, which rearranges thermally to 1,3-di-tert-butyl-2-imidazolidinecarboxaldehyde, 8f, and then to 1,4-di-tert-butyl-2-ketopiperazine, 5f.The reaction of N,N’-diisopropylethylenediamine with glyoxal in water produces 1,4-diisoproyl-2-ketopiperazine, 5e, as the only isolable product.The reaction of a series of N,N’-dialkyl-substituted ethylenediamines with glyoxal in ethanol at low temperature has been found to give a series of cis-trans-cis-1,4,6,9-tetraalkyl-1,4,6,9-tetraaza-5,10-dioxaperhydroanthracenes, 9b,c,e, as minor products.The crystal structure of 9e was determined confirming the stereochemistry of the ring junctures.N,N’-Diphenylethylenediamine reacts with glyoxal to give 1,3-diphenyl-2-imidazolidinecarboxaldehyde, 8d. 8d shows no tendency to rearrange to 5d.A modified reaction scheme or the reaction of N,N’-disubstituted ethylenediamines with glyoxal is presented which accounts for the formation of these new types of products.

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2-Diphenylphosphanyl-1,3,2-diazaphospholidines were prepared via metathesis from 2-chloro-1,3,2-diazaphospholidines and LiPPh2. For some of the products, symmetrisation to tetraphenyldiphosphane and 2,2?-bis-1,3,2- diazaphospholidinyls was observed. Most of the derivatives were characterised by single-crystal X-ray diffraction, which showed that all compounds studied feature elongated exocyclic P-Cl or P-P-bonds, respectively. The extent of this bond lengthening is in the P-phosphanyl-substituted species similar and in the P-chloro-derivatives less pronounced than in corresponding CC-unsaturated 1,3,2-diazaphospholenes. Structure correlation involving comparison of exocyclic P-X and endocyclic P-N distances suggests that n(N)/sigma(P-X) hyperconjugation contributes strongly to the bond lengthening and induces a perceptible weakening of the P-P bonds in 2-diphenylphosphanyl-1,3,2- diazaphospholidines, which should render these compounds interesting substrates for P-P bond activation reactions. Copyright

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A convenient one-pot synthesis of symmetric vicinal diamines utilizing sodium borohydride/trifluoroacetic acid reduction methodology is described.

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A nitrile oxide based route to 2-beta-D-ribofuranosylbenzazoles has been developed. Tri-O-benzoyl-beta-D-ribofuranosylformonitrile oxide (14) was generated from the corresponding carbaldoxime 16 by treatment with NCS/pyridine, followed by base-induced dehydrochlorination of the resulting hydroximoyl chloride. Reaction of the nitrile oxide with 1,2-diaminobenzene afforded 2-(tri-O-benzoyl-beta-D-ribofuranosyl)benzimidazole (21), from which 2-(beta-D-ribofuranosyl)benzimidazole (22) was prepared by treatment with Et3N/MeOH. 2-Aminophenol reacted similarly to yield 2-(tri-O-benzoyl-beta-D- ribofuranosyl)benzoxazole (18). In the absence of a co-reactant dimerisation of the nitrile oxide afforded 3,4-di(tri-O-benzoyl-beta-D-ribofuranosyl)-1,2,5- oxadiazole-2-oxide (17). The carbaldoxime starting material 16 was prepared from tri-O-benzoyl-beta-D-ribofuranosyl cyanide by reaction with semicarbazide to form the semicarbazone, followed by transimination with hydroxylamine.

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Metal catalyst and ligand design,
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The hormone 1alpha,25-dihydroxyvitamin D (1alpha,25(OH)2D) inhibits growth and induces differentiation of prostate cells. The enzyme responsible for 1alpha,25(OH)2D synthesis, 25-hydroxyvitamin D (25(OH)D)-1alpha-hydroxylase (1alpha-OHase), has been demonstrated in human prostate cells. We compared the levels of 1alpha-OHase activity in prostate cancer cell lines, LNCaP, DU145 and PC-3 and in primary cultures of normal, cancerous and benign prostatic hyperplasia (BPH) prostate cells. We observed a marked decrease in 1alpha-OHase activity in prostate cancer cells, including an undetectable level of activity in LNCaP cells. Transient or stable transfection of 1alpha-OHase cDNA into LNCaP cells increased 1alpha-OHase activity from undetectable to 4.95pmole/mg±0.69pmole/mg and 5.8pmole/mg±0.7pmole/mg protein per hour, respectively. In response to 25(OH)D, the prohormone of 1alpha,25(OH)2D, the transfected LNCaP cells showed a significant inhibition of 3H-thymidine incorporation (37%±6% and 56%±4% at 10-8M for transiently and stably transfected cells, respectively). These findings support an important autocrine role for 1alpha,25(OH)2D in the prostate and suggest that the re-introduction of the 1alpha-OHase gene to prostate cancer cells, in conjunction with the systemic administration of 25(OH)D, constitutes an endocrine form of gene therapy that may be less toxic than the systemic administration of 1alpha,25(OH)2D.

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A series of donor- and acceptor-substituted ruthenium cyclopentadienone complexes were synthesized and their catalytic activities towards propargyl alcohols focused on amination reactions have been investigated. It is shown that the substituents of the cyclopentadienone ligand determine the mode of activation of propargyl alcohols by these complexes leading to different central intermediates in catalytic cycles. Catalytic transformations of propargyl alcohols to alpha- or beta-amino ketones, enamino ketones, alpha,beta-unsaturated imines, ketones, alkenes and conjugated enynes could be achieved. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

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Metal catalyst and ligand design,
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Thymidine deoxyoligonucleotides having a 5′-deoxy-5′-methylidyne phosphonate internucleotide linkage were synthesized. Relative to natural DNA, these oligomers were nuclease resistant and formed duplexes with reduced stability.

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Metal catalyst and ligand design,
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