George W. Kabalka

Sonogashira coupling and cyclization reactions on alumina: a route to aryl alkynes, 2-substituted-benzo[b]furans and 2-substituted-indoles

Abstract A solventless, microwave-enhanced Sonogashira coupling reaction of aromatic iodides with terminal alkynes on potassium fluoride doped alumina in the presence of palladium powder, cuprous iodide, and triphenylphosphine has been developed. The reaction can be utilized to prepare aryl alkynes in excellent yields. The coupling of o-iodophenol with terminal alkynes leads to the formation 2-substituted-benzo[b]furans. Whereas the coupling of o-iodoanilines with terminal alkynes generates indole products. An in situ desilylation reaction was also developed.

Rapid microwave-enhanced, solventless Sonogashira coupling reaction on alumina

Abstract A microwave-enhanced, solventless Sonogashira coupling reaction has been developed. Terminal alkynes couple with aryl or alkenyl iodide on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide to provide high yields of products.

Sodium perborate: a mild and convenient reagent for efficiently oxidizing organoboranes

Sodium perborate, a readily available and inexpensive reagent, efficiently oxidizes organoboranes. The reagent permits the oxidation of a wide variety of functionally substituted organoboranes. In nearly every instance, the product yields exceed those obtained using standard oxidation procedures.

The synthesis of radiolabeled compounds via organometallic intermediates

Utilisation de boranes, alanes, silanes, germanes, stannanes, de composes organiques du mercure, de thallates, de reactifs de Grignard, de composes organiques du lithium

SYNTHESES AND SELECTED REDUCTIONS OF CONJUGATED NITROALKENES. A REVIEW

Nitroalkenes have proven to be valuable precursors to a wide variety of target molecules. Several reviews have focused on aliphatic nitro compounds which also encompass nitroalkenes. A few highly specialized reviews have also been written. The present review complements Barretts review and will hopefully stimulate further investigation in the nitroalkene area. Although coverage focuses primarily on the literature since 1980, significant earlier contributions are included. Reactions of nitromethanes have been covered and only a few recent examples are included here.

Rhodium-catalyzed 1,4-addition reactions of diboron reagents to electron deficient olefins

Abstract The 1,4-addition of bis(pinacolato)diboron and bis(neopentyl glycolato)diboron to α,β-unsaturated ketones, esters, nitriles, and aldehydes was developed using a rhodium catalyst.

High resolution computed tomography and MRI for monitoring lung tumor growth in mice undergoing radioimmunotherapy: Correlation with histology

A model lung tumor system has been developed in mice for the evaluation of vascular targeted radioimmunotherapy. In this model, EMT-6 mammary carcinoma tumors growing in the lung are treated with 213Bi, an alpha particle emitter, which is targeted to lung blood vessels using a monoclonal antibody. Smaller tumors (< 100 microm in diameter) are cured, but larger tumors undergo a period of regression and then regrow and ultimately prove lethal. The goal of this work was to determine if external imaging with MRI or CT could be used routinely to monitor the growth/ regression of lung tumors in live mice. To attempt to evaluate individual tumors in vivo, animals were initially imaged with magnetic resonance imaging (MRI). High resolution MRI images could be obtained only after sacrifice when lungs were not moving. In contrast, high resolution computed tomography (CT) produced evaluable images from anesthetized animals. Serial CT images (up to 5/animal) were collected over a 17 day period of tumor growth and treatment. When tumored animals became moribund, animals were sacrificed and lungs were inflated with fixative, embedded in paraffin, and then sectioned serially to compare the detection of tumors by high resolution CT with detection by histology. CT proved most useful in detecting lung tumors located in the hilar area and least useful in detecting serosal surface and anterior lobe tumor foci. Overall, CT images of live animals revealed tumors in approximately 2/3 of cases detected in histologic serial sections when relatively few tumors were present per lung. Detection of lesions and their resolution post therapy were complicated due to residual hemorrhagic, regressing tumor nodules and the development of lung edema both of which appeared as high density areas in the CT scans. We conclude that the microCT method used could identify some lung tumors as small as 100 microm in diameter; however, no concrete evaluation of therapy induced regression of the tumors could be made with CT analyses alone.

The palladium assisted transfer reduction of. alpha. ,. beta. -unsaturated nitroalkenes to oximes using ammonium formate

Abstract α, β-Unsaturated nitroalkenes are readily reduced to the corresponding oximes in good yields using ammonium formate in the presence of palladium. The reactions occur rapidly at room temperature in a solvent system of methanol and tetrahydrofuran.

Transgenic Mouse Model of AA Amyloidosis

AA amyloidosis can be induced in mice experimentally through injection of certain chemical or biological compounds. However, the usefulness of this approach is limited by its dependence on exogenous inflammatory agents that stimulate cytokines to increase the synthesis of precursor serum amyloid A (SAA) protein and the transitory nature of the pathological fibrillar deposits. We now report that transgenic mice carrying the human interleukin 6 gene under the control of the metallothionein-I promoter had markedly increased concentrations of SAA and developed amyloid in the spleen, liver, and kidneys by 3 months of age. At the time of death about 6 months later, organs obtained from these animals had extensive amyloid deposits. This disease process was apparent radiographically using small-animal computer axial tomography and magnetic resonance imaging equipment. The AA nature of the amyloid was evidenced immunohistochemically and was unequivocally established by sequence analysis of protein extracted from the fibrils. The availability of this unique in vivo experimental model of AA amyloidosis provides the means to assess the therapeutic efficacy of agents designed to reduce or prevent the fibrillar deposits found in AA and other types of amyloid-associated disease.

Highly efficient immunoliposomes prepared with a method which is compatible with various lipid compositions

Monoclonal antibody was conjugated to N-glutaryl-phosphatidylethanolamine in the presence of octylglucoside by using N-hydroxysulfosuccinimide as a carboxyl-activation reagent. The conjugated antibody was then incorporated into liposomes by a simple dialysis method. The method is mild and is compatible with various lipid compositions of the liposomes. We have prepared immunoliposomes containing a lung endothelium-specific monoclonal antibody and showed excellent target binding (approximately 75% injected dose) of the immunoliposomes in mouse. Immunoliposomes can be prepared to contain other acidic lipids such as phosphatidylserine and various amounts of cholesterol. The presence of 20% or more cholesterol in liposomes resulted in high level of target binding. We have used in these experiments a new radioactive lipid-phase marker, 111In-DTPA-SA, which was very stable in vivo. The halflife of clearance in mouse exceeded 3 weeks.