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On the basis of the mechanistic insight that more than one Lewis basic moiety (phosphoramide) is involved in the rate- and stereochemistry-determining step of enantioselective allylation, bidentate chiral phosphoramides were developed. Different chiral phosphoramide moieties were connected by tethers of methylene chains of varying length. The rate and enantioselectivity of allylation with allyltrichlorosilane promoted by the bidentate phosphoramides was found to be highly dependent on the tether length. A new phosphoramide based on a 2,2?-bispyrrolidine skeleton has been designed and afforded good yield, efficient turnover, and high enantioselectivity in allylation reactions. The synthesis of enantiopure 2,2?-bispyrrolidine was easily accomplished on large scale by photodimerization of pyrrolidine followed by resolution with L(or D)-tartaric acid. The scope of the allylation reaction was examined with variously substituted allylic trichlorosilanes and unsaturated aldehydes. This method has been applied to the construction of stereogenic, quaternary centers by the addition of unsymmetrically gamma-disubstituted allylic trichlorosilanes.

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Metal catalyst and ligand design,
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A series of p-nitroanisole-containing tetraazacrown (14-18), diazacryptand (22), and diazadithia-crown (23-25) macrocycles has been prepared by treating the appropriate secondary diamine, diazacrown, or dimercaptan with 2,6-bis[(2-chloroacetamido)methyl]-4-nitroanisole (BB). Five of these p-nitroanisole-containing macrocycles were reported earlier. Four new bis(p-nitroanisole)-containing macrocycles resulting from a 2 + 2 macrocyclization of diamine or dimercaptan with BB were also isolated. Six of the p-nitroanisole-containing macrocycles (16, 17, 22-25) were converted to the p-nitrophenol-containing macrocycles (27-32) on treatment with LiI in refluxing pyridine. Thermodynamic quantities (log K, DeltaH, and TAS) for the interactions of four new compounds (24, 27, 31, and 32) with Na+, K+, Ba2+, Ag+, and Pb2+ were evaluated by calorimetric titration at 25.0 C in either 70% or absolute methanol solution. The compounds show strong interactions with Ag+ and Pb2+ but very weak interactions with Na+, K+, and Ba2+. Ligand 31 exhibited high selectivity for Ag+ over Pb2+. X-ray crystal structures were obtained for diazadithia macrocycle 23 and the Ag+-31 complex.

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Metal catalyst and ligand design,
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The present invention relates to respiratory formulations comprising a compound of formula (I): and use of said compounds and compositions in treatment, for example in the treatment of an inflammatory disease or a respiratory disorder, in particular an inflammatory mediated and/or virally mediated respiratory disorder such as asthma and COPD or the treatment or prevention of viral infection, for example infection by influenza virus, rhinovirus or RSV. The invention also extends to certain novel compounds of formula (I).

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Chiral N,N?-dialkylated cyclohexanediamine derived ligands have been synthesized and used in the asymmetric hydrogenation of aryl ketones. Optically active alcohols with up to 90% enantiomeric excess were obtained in high yields.

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PROCESS FOR THE PREPARATION OF CERTAIN TRIARYL RHAMNOSE CARBAMATES

Aryl boronic esters containing the rhamnose carbamate moiety are prepared in good yield and without cleavage of the carbamate linkage by first contacting p-bromophenyl isocyanate with a tetrahydropyran-2-ol followed by reaction with a diboron compound.

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Two aspects of the desymmetrization of selected prochiral aromatic or vinylic dihalides: enantioselective halogen-lithium exchange and prochiral recognition in chiral liquid crystals

Several classes of prochiral dihalides have been identified as potential candidates for asymmetric halogen-lithium exchange. Bis-aryl compounds 1 and 2, 2,3-dibromonorbornadiene 3, and 1,2-diiodoferrocene 4 were prepared and used as substrates in the asymmetric halogen-lithium exchange reaction. The enantioselective mono-lithiation was achieved in good yields by various combinations of n-BuLi and chiral ligands. Enantioselectivities in the range of 20-35% ee have been detected for this new type of asymmetric synthesis. The prochiral compounds 3 and 4 were also dissolved in a chiral liquid crystal based on organic solutions of poly-gamma-benzyl-l-glutamate and analyzed using natural abundance deuterium 2D NMR spectroscopy. The spectroscopic discrimination of enantiotopic sites in these solutes has been observed and discussed from the point of view of orientational order.

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An efficient synthesis of enantiomerically pure trans-N1,N 2-dimethylcyclohexane-1,2-diamine

A new pathway is described to produce a highly optically pure isomer of trans-N1,N2-dimethylcyclohexane-1,2-diamine through four simple steps. Reaction of cyclohexene oxide with aqueous methylamine, followed by cyclisation with Mitsunobu reagent and ring-opening reactions gave rac-trans-N1,N2-dimethylcyclohexane-1,2-diamine, and the enantiomers were obtained via a kinetic resolution using tartaric acid.

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Metal catalyst and ligand design,
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Polystyrenes with chiral phosphoramide substituents as Lewis base catalysts for asymmetric addition of allyltrichlorosilane: Enhancement of catalytic performance by polymer effect

In the asymmetric addition of allyltrichlorosilane to benzaldehyde, polystyrenes with chiral phosphoramide substituents as Lewis base catalysts showed up to 2.4 times better catalytic activity and 1.4 times higher enantioselectivity than the corresponding low-molecular-weight analogues. The Royal Society of Chemistry 2005.

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Metal catalyst and ligand design,
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Unprecedented (eta5-Formylcyclohexadienyl)Mn(CO)3 complexes: Synthesis, structural and theoretical characterizations, and resolution of the planar chirality

The synthesis of the (eta5-formylcyclohexadienyl)Mn(CO) 3 complexes 5-8 was successfully achieved after lithiation and then electrophilic quench by DMF of variously substituted (eta-cyclohexadienyl) Mn(CO)3 complexes. Their full experimental characterization is reported, together with a theoretical study that allowed the consequences of the regiochemistry on the electronic properties of the complexes to be understood. Rearomatization of complex 6 led to the formation of the cationic [(eta6-2-methoxybenzaldehyde)Mn(CO)3]+ complex 11, first example of a benzaldehyde derivative coordinated to the Mn(CO)3+ entity. The electrophilic reactivity of the formyl group of complex 5 was tested with hydrides and a Grignard reagent as the nucleophiles. The corresponding alcohols were isolated in high yields and the excellent diastereoselectivity could be explained by steric factors clearly identified thanks to the crystal structure determination of the starting aldehyde 7b. By using the enantiopure (R,R)-N,N?-dimethylcyclohexane-1,2- diamine, the corresponding aminals were obtained and their resolution afforded, after acidic treatment, the enantioenriched (eta5- formylcyclohexadienyl)Mn(CO)3 with very high enantiomeric excess. The X-ray analysis of two of these aminals 14 and 15 allowed the assignment of the absolute configurations of the planar chiral eta5 moieties.

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SUBSTITUTED ALKYNYLENE COMPOUNDS AS ANTICANCER AGENTS

The present invention relates to substituted alkynylene compounds represented by compound of formula (I) pharmaceutically acceptable salts and stereoisomers thereof. The present invention further provides the methods of preparation of compound of formula (I) and therapeutic uses thereof as anti-cancer agents.

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