Novel and efficient access to phenylamino-pyrimidine type protein kinase C inhibitors utilizing a Negishi cross-coupling strategy

A novel, short, and efficient synthetic pathway to 3-{4-[2-(3-chlorophenylamino)-pyrimidin-4-yl]-pyridin-2-ylamino}-propanol (CGP 60474) and a series of analogues was developed. The synthetic sequence consisted of a Negishi-type cross-coupling reaction in the key step followed by two subsequent nucleophilic substitution reactions. This strategy represents a versatile and robust protocol to access diverse analogues of the title compound for subsequent SAR studies as potential phenylamino-pyrimidine type protein kinase C inhibitors.     

2‐Hydroxy‐3‐(3‐oxobut­yl)naphthalene‐1,4‐dione

The title compound, C₁₄H₁₂O₄, forms crystals which appear monoclinic but are actually twinned triclinic. The asymmetric unit consists of two similar mol­ecules, which differ only in the conformation of the 3‐oxobutyl side chain. The mol­ecular conformation is characterized by an intra­molecular O—H⋯O hydrogen bond between the hydroxy group and the adjacent carbonyl O atom. The crystal structure is stabilized by O—H⋯O hydrogen bonds connecting the mol­ecules into zigzag chains running along the b axis.     

Adduct ion formation by metal complexes under methane negative chemical ionization conditions

Negative chemical ionization mass spectrometry is used as a probe to examine reactions between hydrocarbon radicals and metal complexes in the gas phase. The methane negative chemical ionization mass spectra of 27 complexes of cobalt(II ), nickel(II ) and copper(II ) in the presence of O₄, O₂N₂ and N₄ donor atom sets are characterized by two dominant series of adduct ions of the form [M + C_nH_2n]^? and [M + C_nH_2n+1]^? at m/z values above the molecular ion, [M]^?. Insertion of the CH radical into the ligand followed by radical/radical recombination and electron capture is proposed as the major mechanism leading to the formation of [M + C_nH_2n]^? adduct ions. A second pathway involves ligand substitution by C_nH_2n+1 radicals concomitant with H elimination and electron capture. Oxidative addition at the metal followed by ionization is suggested as the principal pathway for the formation of [M + C_nH_2n+1]^? adduct ions.     

Eine Methode zur präparativen Herstellung markierter Trinukleotide

Zusammenfassung Für ein neues Verfahren zur Untersuchung von Codon—Anticodon-Wechselwirkungen wurden radioaktive Trinukleotide mit möglichst hohen spezif. Aktivitäten im Milligrammaßstab benötigt. Zu ihrer Gewinnung wurde ausE. coli und Bäckerhefe, die in³²P-phosphathältigen Nährmedien gezüchtet worden waren, die Gesamt-RNA isoliert und enzymatisch hydrolysiert. Das dabei entstandene Oligonukleotidgemisch wurde durch Papierchromatographie und Elektrophorese aufgetrennt, wobei elf markierte Trinukleotide in reiner Form erhalten werden konnten.

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For the study of codon-anticodon interactions radioactive trinucleotides with high specific activities had to be prepared in milligram quantities. Labelled RNA was obtained fromE. coli and baker's yeast grown in a medium containing³²P-phosphate. The RNA was hydrolyzed with enzymes and the resulting oligonucleotide mixture separated by paper chromatography and electrophoresis. Eleven pure, labelled trinucleotides were isolated by this procedure.

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Model basis states for photons and "empty waves"

From the perspective of physical realism (PR), a photon is a localized entity that carries energy and momentum, and which is surrounded by a wave packet (anempty wave) that is devoid of observable energy or momentum. In creating quantized PR basis states for a photon wave packet, three requirements must be met:(1) The basis states must each carry the frequency of the wave;(2) They must closely resemble the photon, so that e.g. they scatter in the same manner from an optical mirror;(3) They must have infinitesimal energy, linear momentum, and angular momentum. An essentially zero-energy "empty wave" quantum-a "zeron"-is defined which meets these requirements. It is created as an asymmetric single-particle (or single-antiparticle) excitation of the vacuum state, with the "particle" (or "antiparticle") and its associated "hole" (or "antihole") forming a rotational bound state. The photon is reproduced as a symmetric particle-antiparticle excitation of the vacuum state, with the "particle" and "antiparticle" also forming a rotational bound state. The relativistic transformation problem is discussed. A key point in this development is the deduction of the correct equation of motion for a "hole" state in an external electrostatic field.     

Xanthene dye functionalized norbornenes for the use in ring opening metathesis polymerization

A convenient synthetic route towards polymerizable fluorescein, dicholorofluorescein, and eosin dyes is presented. Polymerizability was provided by linking 2‐norbornene carboxylic acid, 11‐bromo‐undecyl ester to the dye's carboxylate functionality. Although the monomers bearing dichlorofluorescein and eosin were obtained in high yield, the related fluorescein bearing monomer could only be obtained in low yield. In the latter case, concurring etherification and esterification led to a product mixture of the desired carboxy modified monomer and a double substituted by‐product. The dye‐monomers were used successfully for the preparation of statistical copolymers with endo,exo‐2,3‐norbornene dicarboxylic acid dimethylester by ROMP. Absorption and luminescence characteristics and, in particular, the acid/base sensitive behavior of the parent dyes were preserved in the monomers and copolymers. The absorption and emission maxima in THF solution and in the solid state were red shifted in comparison to the aqueous samples of the parent dyes. Dye‐copolymers exhibited good film forming properties. Solid state luminescence studies of the copolymers revealed an increasing sensitivity towards NEt₃ vapor in the order fluorescein < dichlorofluorescein < eosin bearing copolymer. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1336–1348, 2007     

General preservers of invariant subspace lattices

Let be the space of all bounded linear operators on a Banach space X and let LatA be the lattice of invariant subspaces of the operator . We characterize some maps with one of the following preserving properties: Lat(Φ(A)+Φ(B))=Lat(A+B), or Lat(Φ(A)Φ(B))=Lat(AB), or Lat(Φ(A)Φ(B)+Φ(B)Φ(A))=Lat(AB+BA), or Lat(Φ(A)Φ(B)Φ(A))=Lat(ABA), or Lat([Φ(A),Φ(B)])=Lat([A,B]).     

Kinetic electron emission due to perpendicular impact of carbon ions on tungsten surfaces

Total electron yields for perpendicular impact of C⁺ ions on W have been measured for projectile energies from 0.2 keV to 7 keV. The data are compared with the data of C⁺ bombardment of gold and graphite in order to demonstrate general trends in kinetic electron yields at low projectile velocities. The total electron yields in the studied combinations of projectiles and substrates show a similar exponential dependence Γ ∝ (v/A) exp(−A/v), where A is a constant and v is the projectile velocity.