Synthesis and antimalarial effects of N,N-dialkyl-6-(substituted phenyl)-1,2,4,5-tetrazin-3-amines

The synthesis of a series of N,N-dialkyl-6-(substituted phenyl)-1,2,4,5-tetrazin-3-amines (IV) by two routes is described. The first route (Scheme I) involved the oxidative cyclization of formazans (II) to 3-bromo-6-(substituted phenyl)-1,2,4,5-tetrazines (III), followed by treatment with amines. The second (Scheme II) utilized the treatment of 3-(methylthio)-6-(substituted phenyl)-1,2,4,5-tetrazines (VII) with amines to provide the desired products. The intermediate 3-(methylthio)-6-(substituted phenyl)-1,2,4,5-tetrazines (VII) were obtained by thiobenzoylation of hydrazinecarbohydrazonothioic acid methyl ester with [[(substituted phenyl)thioxomethyl]thio]-acetic acids (V) to afford the 1,2-dihydro-3-(methylthio)-6-(substituted phenyl)-1,2,4,5-tetrazines (VI). Oxidation with bromine in acetic acid provided the desired intermediates. The target 6-(substituted phenyl)-1,2,4,5-tetrazin-3-amines (IV) displayed modest antimalarial activity.     

Enantioselective synthesis of rigid 2-aminotetralins. Utility of silicon as an oxygen and nitrogen surrogate in the tandem addition reaction

Dimethylphenylsilyllithium undergoes a highly diastereoselective conjugate addition to chiral naphthyloxazoline 11. Electrophilic trapping of the resulting aza-enolate affords the tandem addition product (12) in high yields as a single diastereomer. The silicon, thus incorporated, may be protodesilylated and undergoes a Tamao oxidation to afford the corresponding alcohol. By chemical modification of the oxazoline, both the gamma-lactone (28) and the delta-lactone (37) were prepared. Reduction of each lactone followed by oxidation of the ensuing diol gave the keto aldehyde. Double reductive amination of the 1,4-dicarbonyl (from the gamma-lactone) allowed the synthesis of two novel hexahydrobenz[e]indoles, 20 and 35. Double reductive amination of the 1,5-dicarbonyl (from the delta-lactone) gave access to two novel octahydrobenzo[f]quinolines, 41 and 43. An unprecedented rearrangement of nitro alcohol 26 into lactone 28 is described and a reasonable mechanism for its formation postulated.     

A long conduction time compact torus plasma opening switch

Experiments to form and accelerate compact toroid (CT) plasmas have been performed on the 0.4-MJ Shiva Star fast capacitor bank at Phillips Laboratory. Theoretical investigations of employing a CT as a very fast opening switch are reported. A particular axisymmetric, geometrically complex switch design is studied with the help of 2-1/2-dimensional magnetohydrodynamic computer simulations. This design, called a magnetically-confined-plasma opening switch (McPOS), accumulates magnetic energy in an inductive store. Because of its intrinsic stability, the switch can conduct current for ten or more microseconds and can open in less than 100 ns-substantially less than the risetime of the capacitively produced electric current. A long conduction time compact torus plasma opening switch     

Ex vivo study of carotid endarterectomy specimens: quantitative relaxation times within atherosclerotic plaque tissues

Purpose

Previous studies reporting relaxation times within atherosclerotic plaque have typically used dedicated small-bore high-field systems and small sample sizes. This study reports quantitative T₁, T₂ and T₂^? relaxation times within plaque tissue at 1.5 T using spatially co-matched histology to determine tissue constituents.

Methods

Ten carotid endarterectomy specimens were removed from patients with advanced atherosclerosis. Imaging was performed on a 1.5-T whole-body scanner using a custom built 10-mm diameter receive-only solenoid coil. A protocol was defined to allow subsequent computation of T₁, T₂ and T₂^? relaxation times using multi-flip angle spoiled gradient echo, multi-echo fast spin echo and multi-echo gradient echo sequences, respectively. The specimens were subsequently processed for histology and individually sectioned into 2-mm blocks to allow subsequent co-registration. Each imaging sequence was imported into in-house software and displayed alongside the digitized histology sections. Regions of interest were defined to demarcate fibrous cap, connective tissue and lipid/necrotic core at matched slice-locations. Relaxation times were calculated using Levenberg-Marquardt's least squares curve fitting algorithm. A linear-mixed effect model was applied to account for multiple measurements from the same patient and establish if there was a statistically significant difference between the plaque tissue constituents.

Results

T₂ and T₂^? relaxation times were statistically different between all plaque tissues (P=.026 and P=.002 respectively) [T₂: lipid/necrotic core was lower 47±13.7 ms than connective tissue (67±22.5 ms) and fibrous cap (60±13.2 ms); T₂^?: fibrous cap was higher (48±15.5ms) than connective tissue (19±10.6 ms) and lipid/necrotic core (24±8.2 ms)]. T₁ relaxation times were not significantly different (P=.287) [T₁: Fibrous cap: 933±271.9 ms; connective tissue (1002±272.9 ms) and lipid/necrotic core (1044±304.0 ms)]. We were unable to demarcate hemorrhage and calcium following histology processing.

Conclusions

This study demonstrates that there is a significant difference between qT₂ and qT₂^? in plaque tissues types. Derivation of quantitative relaxation times shows promise for determining plaque tissue constituents.     

The waveguide laser: A review

The present article reviews the fundamental physical principles essential to an understanding of waveguide gas and liquid lasers, and the current technological state of these devices. At the present time, waveguide laser transitions span the visible through submillimeter regions of the wavelength spectrum. The introduction discusses the many applications of waveguide lasers and the wide variety of laser configurations that are possible. Section 1 summarizes the properties of modes in hollow dielectric waveguides of circular, rectangular, and planar cross section. Section 2 considers various approaches to optical feedback including internal and external mirror Fabry-Perot type resonators, hollow waveguide distributed feedback structures, and ring-resonant configurations. Section 3 discusses those aspects of molecular kinetic and laser theory pertinent to the design and optimization of waveguide gas lasers such as the scaling laws for discharge-excited gas lasers, molecular models useful in maximizing the oscillation bandwidth, the effects of gas flow rate, and the physics of optically-pumped far-infrared lasers. Finally, a review of the waveguide gas and liquid lasers reported to date is given in Section 4.     

High voltage pulses for high impedance loads using explosive formedfuses

Explosive formed fuses (EFFs) use conducting elements that are deformed by explosive pressure (typically, against dielectric dies). This causes the fuse geometry to change, so that the conducting element cross section decreases. This enables a higher ratio of current conduction to current interrupt time than for normal fuses, and it enables more control of when current interruption occurs. In combination with a suitable output closing switch, EFF's can be used to obtain several hundred kilovolt voltage pulses from inductive stores to drive several ohm loads. With proper choices of inductive store, EFF geometry and material, and output closing switch features, such a voltage pulse can be approximately flat topped for microsecond duration and have a small fraction of microsecond risetime. We present theoretical analysis and circuit simulations which illustrate this, using scaled empirical EFF parameters for inductive stores in the 1 weber flux, several hundred nanohenry range. The circuit simulations were done using MicroCap-IV, with user defined elements. These simulations were done with static inductive stores and with explosive magnetic flux compression generators driving inductive stores     

Implosion of solid liner for compression of field reversedconfiguration

The design and first successful demonstration of an imploding solid liner with height to diameter ratio, radial convergence, and uniformity suitable for compressing a field reversed configuration is discussed. Radiographs indicated a very symmetric implosion with no instability growth, with ~13x radial compression of the inner liner surface prior to impacting a central measurement unit. The implosion kinetic energy was 1.5 megajoules, 34% of the capacitor stored energy of 4.4 megajoules     

Total synthesis of (+)-13-deoxytedanolide

In this communication we describe the first total synthesis of (+)-13-deoxytedanolide, an architecturally complex marine macrolide possessing significant antitumor activity. The cornerstone of the synthesis comprises a highly convergent dithiane coupling used to construct the carbon skeleton, followed by a novel use of the Evans-Tishchenko reduction to oxidize the C(1) aldehyde to an ester in the presence of the oxidatively labile dithiane.