Versatile Synthetic Route to Cycloheximide and Analogues That Potently Inhibit Translation Elongation

Cycloheximide (CHX) is an inhibitor of eukaryotic translation elongation that has played an essential role in the study of protein synthesis. Despite its ubiquity, few studies have been directed towards accessing synthetic CHX derivatives, even though such efforts may lead to protein synthesis inhibitors with improved or alternate properties. Described here is the total synthesis of CHX and analogues, and the establishment of structure–activity relationships (SAR) responsible for translation inhibition. The SAR studies aided the design of more potent compounds, one of which irreversibly blocks ribosomal elongation, preserves polysome profiles, and may be a broadly useful tool for investigating protein synthesis.     

Triple Positive Solutions for Multipoint Conjugate Boundary Value Problems

For the nth order nonlinear differential equation y ⁽ⁿ⁾(t)=f(y(t)), t [0,1], satisfying the multipoint conjugate boundary conditions, y ^(j)(a_i) = 0,1 i k, 0 j n _i - 1, 0 =a ₁ < a ₂ < < a _k = 1, and _i=1 ^k n _i =n, where f: [0, ) is continuous, growth condtions are imposed on f which yield the existence of at least three solutions that belong to a cone.     

A technique for the identification and direct analysis of hexahydro-1,3,5-tris(2-hydroxyethyl)-s-triazine in metalworking fluids using electrospray-mass spectrometry

Hexahydro-1,3,5-tris(2-hydroxyethyl)-s-triazine is a widely used biocide in metalworking fluids that resists direct quantification in many analytical methods due to instability. It can be detected in electrospray-mass spectrometry (ES-MS) due to the formation of a charged and relatively stable adduct with the sodium ion. This adduct produces a distinct ion spectrum via collision-induced fragmentation, which should promote specific detection of the analyte in complex matrices. ES-MS detection of the analyte added to, or already present in, metalworking fluid samples at microg mL(-1) levels is demonstrated. Parameters affecting the formation and detection of the sodium adduct, including choice of solvent, alkalinity, and sodium ion level are explored. Linearity of response in flow injection mode is demonstrated.     

The synthesis of some 3‐acylindoles revisited

A study probing the scope of acylation of indoles with dicarboxylic acids in acetic anhydride has been performed, resulting in products incorporating 3‐acylindole‐ or 1‐acylindole motifs depending on the choice of the acid reactant. Synthetically useful results were only obtained from reactions involving malonic acid or Meldrum's acid. Correlations to previous studies have also been made and discussed.     

Fe Spin crossover materials based on dissymmetrical N4 Schiff bases including 2-pyridyl and 2R-imidazol-4-yl rings: Synthesis,crystal structure and magnetic and Mössbauer properties

The synthesis and characterization of new symmetrical Fe^II complexes, [FeL^A(NCS)₂] (1), and [FeL^Bx(NCS)₂] (2–4), are reported (L^A is the tetradentate Schiff base N,N′-bis(1-pyridin-2-ylethylidene)-2,2-dimethylpropane-1,3-diamine, and L^Bx stands for the family of tetradentate Schiff bases N,N′-bis[(2-R-1H-imidazol-4-yl)methylene]-2,2-dimethylpropane-1,3-diamine, with: R = H for L^B1 in 2, R = Me for L^B2 in 3, and R = Ph for L^B3 in 4). Single-crystal X-ray structures have been determined for 1 (low-spin state at 293 K), 2 (high-spin (HS) state at 200 K), and 3 (HS state at 180 K). These complexes remain in the same spin-state over the whole temperature range [80–400 K]. The dissymmetrical tetradentate Schiff base ligands L^Cx, N-[(2-R₂-1H-imidazol-4-yl)methylene]-N′-(1-pyridin-2-ylethylidene)-2,2-R₁-propane-1,3-diamine (R₁ = H, Me; R₂ = H, Me, Ph), containing both pyridine and imidazole rings were obtained as their [FeL^Cx(NCS)₂] complexes, 5–10, through reaction of the isolated aminal type ligands 2-methyl-2-pyridin-2-ylhexahydropyrimidine (R₁ = H, 5–7) or 2,5,5-trimethyl-2-pyridin-2-ylhexahydropyrimidine (R₁ = Me, 8–10) with imidazole-4-carboxaldehyde (R₂ = H: 5, 8), 2-methylimidazole-4-carboxaldehyde (R₂ = Me: 6, 9), and 2-phenyl-imidazole-4-carboxaldehyde (R₂ = Ph: 7, 10) in the presence of iron(II) thiocyanate. Together with the single-crystal X-ray structures of 7 and 9, variable-temperature magnetic susceptibility and Mössbauer studies of 5–10 showed that it is possible to tune the spin crossover properties in the [FeL^Cx(NCS)₂] series by changing the 2-imidazole and/or C2-propylene susbtituent of L^Cx.     

Existence of solutions for three-point boundary value problems for second order equations

Shooting methods are employed to obtain solutions of the three-point boundary value problem for the second order equation, where is continuous, and and conditions are imposed implying that solutions of such problems are unique, when they exist.