Search

Natural cinchona alkaloids were studied to determine the rate of Pt/A12O3-catalyzed hydrogenation of ethyl pyruvate.

We demonstrate real-time detection of self-interfering electrons in a double quantum dot embedded in an Aharonov-Bohm interferometer, with visibility approaching unity. We use a quantum point contact as a charge detector to perform time-resolved measurements of single-electron tunneling. With increased bias voltage, the quantum point contact exerts a back-action on the interferometer leading to decoherence. We attribute this to emission of radiation from the quantum point contact, which drives noncoherent electronic transitions in the quantum dots.

This Account records work carried out in our laboratories during the last 2 decades in the field of enantioselective heterogeneous hydrogenation. Of particular interest was Orito's catalytic system, platinum catalysts modified with cinchona alkaloids for the hydrogenation of activated ketones. Described are the development of the optimal platinum catalyst and modifier and the expansion of the scope of the catalyst. Kinetic studies aimed at understanding the mode of action of the catalyst revealed that the cinchona modifier not only renders the catalyst enantioselective but strongly accelerates the hydrogenation. This was the first case of ligand acceleration with a heterogeneous catalytic system. Finally, a number of industrial processes are summarized with the enantioselective hydrogenation of various alpha-keto esters as a key step.

The parallel carbonylation of aryl halides with 6-25 bar of CO in 1-mL vials in a standard autoclave was investigated. 4-Bromoacetophenone and 2-chloropyridine were used as model substrates with 102 different O-nucleophiles (primary and secondary alcohols, phenols). No inertization during the loading was necessary. Fifty esters (43 new, yield up to 60%) were isolated and characterized. Ether, ester, ketone, and sometimes even olefin functions were usually tolerated. The new method is suitable for screening and small scale products synthesis.

Palladacycle dimers possessing bridging halides can be easily cleaved by using N-heterocyclic carbenes (NHCs) to generate novel monomeric complexes. The structure of one of these was determined by single-crystal diffraction study and consists of a square-planar coordination around the palladium center where the NHC ligand is trans to the amine of the palladacycle. The complex was found to be equally active in aryl amination and alpha-arylation of ketones even at very low catalyst loading (0.02 mol %). Primary and secondary alkyl/arylamines are equally active partners in coupling reactions. [reaction: see text]

Primary aromatic amides were prepared by a palladium-catalyzed aminocarbonylation reaction of aryl halides in high yields (70-90%) using formamide as the amine source. The reactions require a palladium catalyst in combination with a nucleophilic Lewis base such as imidazole or 4-(dimethylamino)pyridine (DMAP). Aryl, heteroaryl, and vinyl bromides and chlorides were converted to the primary amides under mild conditions (5 bar, 120 degrees C) using 1 mol % of a palladium-phosphine complex. Best results were obtained in dioxane using triphenylphosphine as the ligand and DMAP as the base. For activated aryl bromides, a phosphine-to-palladium ratio of 2:1 was sufficient, but less reactive aryl bromides or aryl chlorides required ligand-to-palladium ratios up to 8:1 in order to stabilize the catalyst and achieve full conversion. The influence of catalyst, base, solvent, pressure, and temperature was studied in detail. The mechanism of the reaction could be clarified by isolating and identifying the reaction intermediates. In addition, methylamides and dimethylamides were prepared by the same method using N-methylformamide and N,N-dimethylformamide as the amine source.

Insight into the metabolism of radiolabeled antibodies is important for the design of better radioimaging and therapy agents. To test the effect of linkers that can be cleaved in vivo, we introduced Ala-Leu-Ala-Leu between the antibody Lym-1 and an 111In-labeled benzyl-EDTA. For comparison, we studied a conjugate without the linker. Digestion of the two conjugates in vitro showed that the one with Ala-Leu-Ala-Leu was cleaved rapidly by the liver protease cathepsin B1 (T1/2 approximately 6 h). After 100 h of digestion, reversed-phase HPLC product analysis of the Ala-Leu-Ala-Leu conjugate showed that 48% of the total radioactivity had the same retention time as (p-aminobenzyl)-EDTA(In), and 37% of the total radioactivity had the same retention time as [p-(Ala-Leu-amido)benzyl]-EDTA(In). After 97 h of digestion, the conjugate without the linker had 79% of the radioactivity activity still attached to the protein. We also tested the two conjugates in mice. Ala-Leu-Ala-Leu had only a moderate effect on the whole body and liver clearance in vivo. The excretion of the radioactivity was about 6% per day with the linker and about 3% per day without the linker. HPLC analysis of the urine of a single mouse showed products similar to the in vitro study; 54% of the excreted radioactivity had the same retention time as (p-aminobenzyl)-EDTA(In), while 10% had the retention time of [p-(Ala-Leu-amido)benzyl]-EDTA(In).

The synthesis of a protected bifunctional analog of ethylenediaminetetraacetic acid (EDTA) is described. The molecule contains an aminobenzyl moiety that allows the easy attachment of the chelating agent to a wide variety of groups. Examples of reaction with the C-termini of two peptides are given. In the following paper, the two peptides are used to study the enzymatic cleavage of metal chelates from a monoclonal antibody.