Intramolecular Diels-Alder Reactions of Decatrienoates: Remote Stereocontrol and Conformational Activation(1)

The intramolecular Diels-Alder (IMDA) reactions of C(8)-substituted decatrienoates have been studied. The stereospecific formation of 11 via an endo-boat-9 transition state attests to the powerful directing influence of a C(8) substituent in the IMDA of decatrienoate. In addition, the contrasting observations that stereospecific 9 --> 11 occurs at room temperature while the nor-tert-butyl substrate (4a) requires 125 degrees C/5 h reaction conditions and produces a 60:40 mixture of diastereomers provide clear evidence that a bulky C(8) substituent is a powerful conformational activator of the IMDA.     

Synthesis of [ethylene-1-(eta(5)-4,5,6,7-tetrahydro-1-indenyl)-2- (eta(5)-4',5',6',7'-tetrahydro-2'-indenyl)]titanium dichloride, the elusive isomer of the Brintzinger-type ansa-titanocenes

We present a short synthesis of 1-(2-indenyl)-2-(3-indenyl)ethane (5) and a method for its conversion to the ansa-metallocene [ethylene(eta5-inden-1-yl)(eta5-inden-2-yl)]titanium dichloride (13). The synthetic strategy applied to prepare bisindene 5 relies on the efficient alkylation of 2-(phenylsulfonyl)indane followed by HMPA-assisted E1cB-elimination of phenylsulfinate. This tandem sequence circumvents the predisposition of indene to undergo C(1)-alkylation and enables access to C(2)-substituted indenes. The key step in the synthesis of the title ansa-titanocene (4) features a previously unreported equilibration step to generate the bis(indenide anion) of 5. Complexation with TiCl4.(THF)2 followed by hydrogenation of the product metallocene furnishes ansa-titanocene 4.     

The solid-phase Zincke reaction: preparation of omega-hydroxy pyridinium salts in the search for CFTR activation

A study of structural modifications of MPB-07 was undertaken as part of a synthetic program aimed at discovering small molecules with CFTR activation potential. Solid-phase synthesis techniques were used to prepare derivatives of MPB-07 employing the Zincke reaction for the construction of aromatic, quaternary ammonium salts such as those found in 2 or 3. In this transformation, primary amines react with highly electrophilic N-2,4-dinitrophenylpyridinium (DNP) salt 4 to afford pyridinium salt 8 with release of 2,4-dinitroaniline 6. Thus, the reaction of 1-(2,4-dinitrophenyl)pyridinium salts with various polymer-bound amino ethers, followed by cleavage from the resin, delivers the desired salts in good yield and high purity.     

Graphical Representations of Speed: Obstacles Preservice K‐8 Teachers Experience

This study examines the difficulties college students experience when creating and interpreting graphs in which speed is one of the variables. Nineteen students, all preservice elementary or middle school teachers, completed an upper‐level course exploring algebraic concepts. Although all of these preservice teachers had previously completed several mathematics courses, including calculus, they demonstrated widespread misconceptions about the variable speed. This study identifies four cognitive obstacles held by the students, provides excerpts of their graphical constructions and verbal interpretations, and discusses potential causes for the confusion. In particular, misconceptions arose when students interpreted the behavior and nature of speed within a graphical context, as well as in situations where they were required to construct a graph involving speed as a variable. The study concludes by offering implications for the teaching and learning of speed and its interpretation within a graphical setting.     

Gold nanoparticle-fluorophore complex for conditionally fluorescing signal mediator

Fluorescent contrast agents with high specificity and sensitivity are valuable for accurate disease detection and diagnosis. Spherical gold nanoparticles (GNPs) can be smartly utilized for developing highly effective agents. The strong electromagnetic (plasmon) field on their surface can be very effective in influencing the electrons of fluorophores and, thus, manipulating the fluorescence output (i.e., either quenching or enhancement). Fluorescence quenching can be used for negative sensing, or for conditional de-quenching to increase the specificity. Fluorescence enhancement allows sensing to be more sensitive. The level of fluorescence alteration depends on the GNP size, the excitation and emission wavelengths and quantum yield of the fluorophore, and the distance between the GNP and the fluorophore. To understand the mechanisms of the fluorescence change by GNP, we have theoretically analyzed the parameters involved in the fluorescence alteration for commonly used fluorophores, with an emphasis on quenching. The results showed that the fluorescence of fluorophores with the excitation (Ex) and emission (Ex) wavelengths close to the GNP resonance peak tended to be significantly quenched by GNPs. For those fluorophores emitting fluorescence in red or near infrared, to achieve quenching, the distance between GNP and the fluorophore was required to be very short. In general, a shorter distance resulted in more quenching. Bigger GNPs require a shorter distance to achieve the same level of quenching. The fluorescence of a fluorophore with a lower quantum yield (especially the one with emission in far-red or near-infrared) is more difficult to be quenched by GNPs (requires very short distance). Instead, it can be enhanced. Based on the theoretical study, we have developed a near-infrared contrast agent, i.e., Cypate conjugated GNP via a short peptide spacer. Normally the fluorescence of Cypate was quenched. The spacer has a motif of a substrate for urokinase type plasminogen activator (uPA; cancer-secreting enzyme). This contrast agent emits fluorescence only in the presence of uPA, where the uPA cleaves the spacer. This design can be used in characterization of the cancer type and also in diagnosing other diseases with signature enzymes.     

The Influence of β-Ammonium Substitution on the Reaction Kinetics of Aminooxy Condensations with Aldehydes and Ketones

The click-chemistry capture of volatile aldehydes and ketones by ammonium aminooxy compounds has proven to be an efficient means of analyzing the carbonyl subset in complex mixtures, such as exhaled breath or environmental air. In this work, we examine the carbonyl condensation reaction kinetics of three aminooxy compounds with varying β-ammonium ion substitution using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). We determined the activation energies for the reactions of the aminooxy compounds ATM, ADMH and AMAH with a panel of ketones and aldehydes that included acrolein and crotonaldehyde. The measurements indicate that the activation energies for the oximation reactions are quite low, less than 75 kJ mol⁻¹. ADMH is observed to react the fastest with the carbonyls studied. We postulate this result may be attributed to the ADMH ammonium proton effecting a Brønsted-Lowry acid-catalyzed elimination of water during the rate-determining step of oxime ether formation. A theoretical study of oxime ether formation is presented to explain the enhanced reactivity of ADMH relative to the tetraalkylammonium analog ATM.     

Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.     

Transannular Anti-Michael Addition: Formation of 4H-Pyrazolo[5,1-c]thiazines

The reaction of 2-(diphenylmethylene)thietan-3-one (2) with 1,2,4,5-tetrazines (3a-c) in KOH/MeOH/THF gives 4H-pyrazolo[5,1-c]thiazines (7a-c). This novel condensation reaction proceeds via the intermediacy of an 8-(diphenylmethylene)-2H-1,4,5-thiadiazocin-7(8H)-one (5), which undergoes a multi-step rearrangement including a rare anti-Michael addition.     

Stereogenic Propargylic Centers via Base-Mediated Terminal Allene Isomerization

A study of alkali metal amide-mediated isomerizations of terminal allenes is described. The isomerizations of substituted ethenylidenecyclohexanes to form diastereomeric mixtures of terminal alkynes have been conducted to determine factors which may influence the stereochemistry at the newly formed propargylic centers. An initial base screen revealed that potassium N-methylbutylamide (KMBA) exhibits the highest level of equatorial to axial alkyne diastereoselectivity. With the severely hindered terminal allene 26, the use of potassium 3-aminopropylamide is required to effect isomerization. A general synthesis of deuterated terminal allenes has also been achieved, and a mechanistic study using d(2)-allenes 18a,b has revealed the involvement of a propargylic anion in the course of the KMBA-mediated isomerizations.