ABSTRACT
Acylstannanes were found to add to such alpha,beta-unsaturated carbonyl compounds as enones or ynoates in the presence of a nicel or palladium catalyst to give 2-stannyl-4-oxoalk-2-enoates or 1,4-diketones, whereas the three component coupling between acylstannanes, enones and aldehydes provided 2-hydroxymethyl 1,4-diketones.
ABSTRACT
Arynes were found to insert into a carbon-tin bond of alkynyl- and vinylstannanes in the presence of a catalytic amount of a palladium-iminophosphine complex to afford ortho-substituted arylstannanes, which were convertible into a wide variety of 1,2-disubstituted arenes via carbon-carbon bond forming reactions.
ABSTRACT
An alpha-methylallylstannane added to an alkyne in the presence of a palladium catalyst with perfect regioselectivity both in the allylic and alkynic moieties. Comparison of the reaction of isomeric butenylstannanes suggests two catalytic cycles, one of which includes a palladacyclopentene intermediate and beta-tin elimination pathway.
ABSTRACT
A series of renin inhibitors containing the (2S,3S,5S)-2-amino-1-cyclohexyl-6-methyl-3,5-heptanediol (2-amino-3,5-anti-diol) fragment as a novel transition-state mimic was synthesized, and their biological activities were evaluated. All of the synthesized compounds containing the 2-amino-3,5-anti-diol fragment at the P1-P1' position showed high in vitro renin-inhibitory activity with IC50 values in the 10(-8)-10(-10) M range, and most of them caused a reduction of blood pressure when administered orally to salt-depleted, conscious marmosets. The inhibitor (29) with the 4-hydroxypiperidine residue at the P4 position showed the highest activity in terms of both potency and duration of the blood pressure-lowering effect.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/chemical synthesis , Antihypertensive Agents/chemical synthesis , Blood Pressure/drug effects , Dipeptides/chemistry , Fatty Alcohols/chemistry , Renin/antagonists & inhibitors , Administration, Oral , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Antihypertensive Agents/pharmacology , Callithrix , Cathepsin D/antagonists & inhibitors , Humans , Magnetic Resonance Spectroscopy , Pepsin A/antagonists & inhibitors , Renin/blood , Renin-Angiotensin System/drug effects , Sodium Chloride , Species Specificity , Spectrometry, Mass, Fast Atom Bombardment , Structure-Activity RelationshipSubject(s)
Arachidonate 12-Lipoxygenase/blood , Arachidonate 15-Lipoxygenase/metabolism , Arachidonate 5-Lipoxygenase/blood , Arachidonic Acids/metabolism , Animals , Cannabinoids/metabolism , Endocannabinoids , Humans , Leukocytes , Oxidation-Reduction , Polyunsaturated Alkamides , Reticulocytes/enzymology , Glycine max/enzymology , SwineABSTRACT
Various purified lipoxygenases were incubated with [14C]arachidonylethanolamide which is an endogenous ligand for cannabinoid receptors. When radioactive products were analyzed by thin-layer chromatography, porcine leukocyte 12-lipoxygenase and rabbit reticulocyte and soybean 15-lipoxygenases produced polar compounds at about the same reaction rates as that of oxygenation of free arachidonic acid. In contrast, the reaction of human platelet 12-lipoxygenase proceeded at a much lower rate, and porcine leukocyte 5-lipoxygenase was totally inactive. The result indicated that the lipoxygenases, which had been shown previously to be capable of oxygenating esterified polyunsaturated fatty acids, were also active with the arachidonylethanolamide. High-performance liquid chromatography, ultraviolet and mass spectrometry and nuclear magnetic resonance spectroscopy identified the major product by leukocyte 12-lipoxygenase as 12-hydroperoxy-5,8,10,14-eicosatetraenoylethanolamide and that by 15-lipoxygenases as 15-hydroperoxy-5,8,11,13-eicosatetraenoylethanolamide. The 15-hydroxy derivative inhibited electrically-evoked contraction of mouse vas deferens with an IC50 of 0.63 microM as well as arachidonylethanolamide (0.17 microM), but the 12-hydroxy derivative was much less effective.
Subject(s)
Arachidonic Acids/metabolism , Lipoxygenase/metabolism , Receptors, Drug/agonists , Animals , Arachidonate 12-Lipoxygenase/metabolism , Arachidonate 15-Lipoxygenase/metabolism , Blood Platelets/enzymology , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Endocannabinoids , Humans , Kinetics , Leukocytes/enzymology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Oxidation-Reduction , Polyunsaturated Alkamides , Rabbits , Receptors, Cannabinoid , Receptors, Drug/metabolism , Reticulocytes/enzymology , Glycine max/enzymology , Spectrophotometry, Ultraviolet , SwineABSTRACT
Compression of the spinal cord due to atlantoaxial subluxation was diagnosed in a patient with Morquio's syndrome and in another with spondyloepiphyseal dysplasia (SED) congenita by cervical radiography and magnetic resonance imaging (MRI). The patient with Morquio's syndrome, a 15 year old boy, had no neurologic symptoms and his somatosensory evoked potential (SSEP) was normal. However, MRI demonstrated spinal cord compression at C1-C2. In contrast, the patient with SED congenita, an 11 year old girl, had neck pain, hyperreflexia and loss of vibration sense in both legs. These findings were explained by the absence of P3 and later waves in SSEP and by compression of the spinal cord observed on MRI. Both SSEP and MRI should be used for evaluating disorders in which atlantoaxial subluxation might be present.
