Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Optically Active Protected Aminocycloheptitols and Bicyclo[4.4.1]undecatriene

The racemic (6-cyclo-heptadienyl)Fe(CO)3+ cation ((±)-7), prepared from cyclooctatetraene, was treated with a variety of carbon and heteroatom nucleophiles. Attack took place at the less hindered C1 dienyl carbon and decomplexation of the (cycloheptadiene)Fe(CO)3 complexes gave products rich in functionality for further synthetic manipulation. In particular, a seven-step route was developed from racemic (6-styryl-2,4-cycloheptadien-1-yl)phthalimide ((±)-9 d) to afford the optically active aminocycloheptitols (−)-20 and (+)-20

Closed Brayton Cycle power system with a high temperature pellet bed reactor heat source for NEP applications

Capitalizing on past and future development of high temperature gas reactor (HTGR) technology, a low mass 15 MWe closed gas turbine cycle power system using a pellet bed reactor heating helium working fluid is proposed for Nuclear Electric Propulsion (NEP) applications. Although the design of this directly coupled system architecture, comprising the reactor/power system/space radiator subsystems, is presented in conceptual form, sufficient detail is included to permit an assessment of overall system performance and mass. Furthermore, an attempt is made to show how tailoring of the main subsystem design characteristics can be utilized to achieve synergistic system level advantages that can lead to improved reliability and enhanced system life while reducing the number of parasitic load driven peripheral subsystems

Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Aminobicyclo[5.1.0]octitols

A series of eight stereoisomeric N-(tetrahydroxy bicyclo-[5.1.0]oct-2S*-yl)phthalimides were prepared in one to four steps from N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide (±)-7, which is readily available from cyclooctatetraene (62 % yield). The structural assignments of the stereoisomers were established by 1H NMR spectral data as well as X-ray crystal structures for certain members. The outcomes of several epoxydiol hydrolyses, particularly ring contraction and enlargement, are of note. The isomeric phthalimides as well as the free amines did not exhibit β-glucosidase inhibitory activity at a concentration of less than 100 μM

Pharmacological characterization of GABAA receptors in taurine-fed mice

<p>Abstract</p> <p>Background</p> <p>Taurine is one of the most abundant free amino acids especially in excitable tissues, with wide physiological actions. Chronic supplementation of taurine in drinking water to mice increases brain excitability mainly through alterations in the inhibitory GABAergic system. These changes include elevated expression level of glutamic acid decarboxylase (GAD) and increased levels of GABA. Additionally we reported that GABA_A receptors were down regulated with chronic administration of taurine. Here, we investigated pharmacologically the functional significance of decreased / or change in subunit composition of the GABA_A receptors by determining the threshold for picrotoxin-induced seizures. Picrotoxin, an antagonist of GABA_A receptors that blocks the channels while in the open state, binds within the pore of the channel between the β2 and β3 subunits. These are the same subunits to which GABA and presumably taurine binds.</p> <p>Methods</p> <p>Two-month-old male FVB/NJ mice were subcutaneously injected with picrotoxin (5 mg kg^-1) and observed for a) latency until seizures began, b) duration of seizures, and c) frequency of seizures. For taurine treatment, mice were either fed taurine in drinking water (0.05%) or injected (43 mg/kg) 15 min prior to picrotoxin injection.</p> <p>Results</p> <p>We found that taurine-fed mice are resistant to picrotoxin-induced seizures when compared to age-matched controls, as measured by increased latency to seizure, decreased occurrence of seizures and reduced mortality rate. In the picrotoxin-treated animals, latency and duration were significantly shorter than in taurine-treated animas. Injection of taurine 15 min before picrotoxin significantly delayed seizure onset, as did chronic administration of taurine in the diet. Further, taurine treatment significantly increased survival rates compared to the picrotoxin-treated mice.</p> <p>Conclusions</p> <p>We suggest that the elevated threshold for picrotoxin-induced seizures in taurine-fed mice is due to the reduced binding sites available for picrotoxin binding due to the reduced expression of the beta subunits of the GABA_A receptor. The delayed effects of picrotoxin after acute taurine injection may indicate that the two molecules are competing for the same binding site on the GABA_A receptor. Thus, taurine-fed mice have a functional alteration in the GABAergic system. These include: increased GAD expression, increased GABA levels, and changes in subunit composition of the GABA_A receptors. Such a finding is relevant in conditions where agonists of GABA_A receptors, such as anesthetics, are administered.</p