Control of electron demand in the cycloadditions of 2(H)-1,4-oxazin-2-ones

3-Methoxy-5-chloro-6-methyl-2(H)-1,4-oxazin-2-one 4, 3-methoxy-5-chloro-6-phenyl-2(H)-1,4-oxazin-2-one 5, 3-phenylsulfenyl-5-chloro-6-methyl-2(H)-1,4-oxazin-2-one 6, and 3-phenylsulfenyl-5-chloro-6-phenyl-2(H)-1,4-oxazin-2-one 7, are ambident dienes and undergo Diels-Alder cycloadditions with electron neutral, rich and deficient dienophiles.     

Kinetic study of the reaction between hydroxylated polybutadienes and isocyanates. 1. Reaction with tolylene diisocyanate (TDI)

A comparative kinetic study of the reaction of three different hydroxylated liquid polybutadienes (M _n ? 3000) — R - 45M, R-45HT, and H-034—and tolylene diisocyanate (TDI), was carried out in toluene solution. An analytical method was used to follow the kinetics of the reactions at four different temperatures. The reactions presented an apparent second-order rate law. In the second-order plots, a discontinuity was observed. The R-45M polybutadiene was about twice more reactive than R-45HT and H-034; these latter two polybutadienes presented similar reactivities.     

Synthesis of 7beta-sulfur analogues of paclitaxel utilizing a novel epimerization of the 7alpha-thiol group

Paclitaxel analogues with a sulfur group at the 7beta position were required for SAR studies. Attempts to generate these compounds by displacing a 7alpha leaving group with sulfur nucleophiles were unsuccessful. Instead, these compounds were successfully prepared from a 7beta-thiol intermediate that was obtained by a base-catalyzed epimerization of the 7alpha-thiol derivative. The epimerization presumably proceeds through a thioaldehyde intermediate and exhibits the opposite stereochemical preference of its oxygen counterpart.     

Resurrection and Reactivation of Acetylcholinesterase and Butyrylcholinesterase

Organophosphorus (OP) nerve agents and pesticides present significant threats to civilian and military populations. OP compounds include the nefarious G and V chemical nerve agents, but more commonly, civilians are exposed to less toxic OP pesticides, resulting in the same negative toxicological effects and thousands of deaths on an annual basis. After decades of research, no new therapeutics have been realized since the mid-1900s. Upon phosphylation of the catalytic serine residue, a process known as inhibition, there is an accumulation of acetylcholine (ACh) in the brain synapses and neuromuscular junctions, leading to a cholinergic crisis and eventually death. Oxime nucleophiles can reactivate select OP-inhibited acetylcholinesterase (AChE). Yet, the fields of reactivation of AChE and butyrylcholinesterase encounter additional challenges as broad-spectrum reactivation of either enzyme is difficult. Additional problems include the ability to cross the blood brain barrier (BBB) and to provide therapy in the central nervous system. Yet another complication arises in a competitive reaction, known as aging, whereby OP-inhibited AChE is converted to an inactive form, which until very recently, had been impossible to reverse to an active, functional form. Evaluations of uncharged oximes and other neutral nucleophiles have been made. Non-oxime reactivators, such as aromatic general bases and Mannich bases, have been developed. The issue of aging, which generates an anionic phosphylated serine residue, has been historically recalcitrant to recovery by any therapeutic approach—that is, until earlier this year. Mannich bases not only serve as reactivators of OP-inhibited AChE, but this class of compounds can also recover activity from the aged form of AChE, a process referred to as resurrection. This review covers the modern efforts to address all of these issues and notes the complexities of therapeutic development along these different lines of research.     

3-Aryl-4-Isoquinolinone Derivatives An Efficient Oxidative Preparation

A comparative study of the oxidation of 3-aryl-4-hydroxytetrahydroisoquinolines has been carried out. A modification of the Jones conditions turn out to be the best methodology for the regioselective preparation of target 4-isoquinolinone derivatives.     

A PASE-based approach towards 12-(1H-1,2,3-triazol-1-yl)-indolo[2,1-a]isoquinolines via the reaction of 3-(isoquinolin-1-yl)-1,2,4-triazines with benzyne

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Generic Fredholm alternative-type results for the one dimensional p-Laplacian

In this paper we give a generic necessary and sufficient condition for the solvability of? Received November 1999     

Optimal Kα XRF detection geometry of arsenic in skin using an extended fundamental parameter method

The fundamental parameter (FP) method was extended to account for the geometrical details of experimental x‐ray fluorescence (XRF) detection. In the traditional FP method the primary fluorescence photons have parallel pathways towards the detector. In the new approach the primary fluorescence photons can travel in any direction which allows them to reach the detector if not absorbed or scattered. The derived XRF signal equation explicitly depends on the length of the collimator in front of the detector, the detector size, position and orientation. An algorithm which numerically calculates the XRF signal for any set of parameters was developed and implemented for the K_α XRF signal of arsenic in skin. Optimal positions and orientations of the detector and collimator ensemble which maximize the XRF signal were found. Results and limitations of the method were also discussed. Copyright © 2009 John Wiley & Sons, Ltd.