The chemistry of wine polyphenolic C-glycosidic ellagitannins targeting human topoisomerase II

Polyphenolic nonahydroxyterphenoyl-containing C-glycosidic oak ellagitannins are found in wine as a result of the aging of this beverage in oak-made barrels. Once in the slightly acidic wine (pH approximately 3-4), some of these complex natural products such as (-)-vescalagin (1), but not its C-1 epimer (-)-castalagin (2), can capture grape-derived nucleophilic entities such as ethanol, the flavanols catechin (10a) and epicatechin (10b), the anthocyanin oenin (13b), and the thiolic glutathione (16) to furnish condensation products with retention of configuration at the C-1 locus. A computer-aided rationale of this high diastereoselectivity is given. These condensation products can contribute to the modulation of organoleptic properties of the wine, as evidenced by the 23 nm bathochromic shift color absorbance observed with the novel oenin-based anthocyano-ellagitannin (15b). Hydrolysis of 1 under solvolytic conditions furnished another novel compound that we refer to as vescalene (21), in addition to the known (-)-vescalin (18). Of pharmacological importance is the fact that most of these found-in-wine water-soluble ellagitannin derivatives are much more potent than etoposide (VP-16) at inhibiting top2-mediated DNA decatenation in vitro (top2=topoisomerase II)). The known (-)-vescalin (18) and the novel vescalene (21) fully inhibited top2 at 10 microM concentration!     

Convenient Synthesis of Alkenyl‐, Alkynyl‐, and Allenyl‐Substituted Imidazo[1,2‐a]pyridines via Palladium‐Catalyzed Cross‐Coupling Reactions

A systematic study on the Stille and Sonogashira cross‐coupling of iodinated imidazo[1,2‐a]pyridines was performed, permitting the preparation of various vinyl‐, ethynyl‐, and allenyl‐substituted derivatives. These methods are particularly valuable, given their experimental simplicity and high degree of flexibility with regard to functional groups that can be introduced in positions 3, 6, or 8 of the imidazo[1,2‐a]pyridine core. Effects concerning different substitution positions and the nature of the 2‐substituent under various reaction conditions are reported in detail for the above types of unsaturated groups introduced.     

Half-projected and projected Hartree-Fock calculations for singlet ground states. II. Lithium hydride

The half-projected Hartree–Fock function (HPHF ) for singlet states is defined as a linear combination of two Slater determinants which contains only spin eigenstates with even spin quantum numbers. The possible uses of such an approach for determining molecular properties are investigated computing the potential energy curve, binding energy, force constant, and dipole moment variation corresponding to the lithium hydride ground state. Full projected and restricted Hartree–Fock calculations (PHF and RHF ) are performed simultaneously for comparison purposes. It is found that the HPHF model yields very satisfactory results, very close to those of the PHF scheme. Both models predict properly the molecular behavior as a function of nuclear separation, whereas the RHF one fails. A discussion is given in terms of configuration equivalents. It is concluded that the HPHF scheme seems to be useful for determining molecular properties specially in the case of large systems in which the more sophisticated methods are unmanageable.     

Synthese de polyphosphonates et polyphosphonamides a partir de monomeres diphosphoniques polycondensation en solution

Synthesis of linear polyphosphonates and polyphosphonamides is achieved by polycondensation in solution of aromatic diols and diamines with alkyldiphosphonyl tetrachlorides, in the presence of a hydrochloric acid trapping agent (triethylamine). The main limiting factors for chain growth are the insolubility of the polymers and the occurrence of side reactions.     

In situ formation of C-glycosides during electrospray ionization tandem mass spectrometry of a series of synthetic amphiphilic cholesteryl polyethoxy neoglycolipids containing <Emphasis Type="Italic">N</Emphasis>-acetyl-D-glucosamine

In this communication, the structural analysis of six synthetic O-Linked amphiphilic cholesteryl polyethoxy neoglycolipids containing N-acetyl-D-glucosamine was performed by electrospray ionization mass spectrometry in the positive ion mode, with a QqTOF-MS/MS hybrid instrument. The MS/MS analyses provided evidence for the "in situ" formation, in the collision cell of the tandem mass spectrometer, of an unexpected and unique [C-glycoside]+ product ion, resulting from an ion-molecule reaction between the N-acetyl-D-glucosamine oxonium ion and the neutral cholesta-3,5-diene molecule. Quasi MS3 analysis of this ion resulted in the dissociation of the precursor [C-glycoside]+ ion, which produced the expected third generation N-acetyl-D-glucosamine oxonium and the protonated cholesta-3,5-diene product ions.     

Oriented binding of the His6-tagged carboxyl-tail of the L-type Ca2+ channel alpha1-subunit to a new NTA-functionalized self-assembled monolayer

Oriented stable binding of functional proteins on surfaces is of fundamental interest for receptor/ligand studies in atomic force microscopy (AFM) and surface plasmon resonance (SPR) experiments. Here we have chosen the His6-tagged carboxyl-tail (C-tail) of the alpha1c-subunit of the L-type Ca2+ channel and calmodulin (CaM) as its cognitive partner as a model system to develop a new functional surface. Covalently attached self-assembled monolayers on ultraflat gold containing NTA-thiols to which the His6-tagged C-tail was bound and thiols with triethylene-glycol groups as matrix-thiols represented the system of choice. The topography of this surface was characterized using AFM; its ability to bind C-tail proteins oriented and stable was confirmed by SPR measurements and by complementary force spectroscopy experiments with a CaM4-construct covalently attached to the tip. The developed anchoring strategy can now be used to study receptor/ligand interactions in general applying force spectroscopy and SPR on His6-tagged proteins oriented immobilized onto this new NTA-functionalized self-assembled monolayer.     

Etude de nouveaux systemes aromatiques possédant des propriétes diéniques: [2]benzothiéno[5,6-g] phtalazines,thiéno[3,4-g]phtalazines et leurs analogues furanniques

Derivatives of new polydienic systems have been isolated. Two [2]benzothienophthalazines, nitrogenous analogues of unknown anthra[2,3-c]thiophens are described. A furo[3,4-g]-phtalazine and a thieno[3,4-g]phthalazine are isolated. These different compounds react with philodienes. The first tetraza-2,3,8,9-naphthacenes have been synthesized. Structures of these compounds are proved by chemical and spectrographical methods.     

A solid-state spectral effect in eclipsed tetracyanonickelates: X-ray crystal structure, polarized specular reflectance spectroscopy, and ZINDO modeling of Sr[Ni(CN)4].5H2O, Rb2[Ni(CN)4].H2O, and Na2[Ni(CN)4].3H2O

Crystal structures of three Ni(CN)(4)(2)(-) salts all with eclipsed ligands and varying axial stacking arrangements are presented. The absorption spectra of all three salts show a slight red shift in the x,y-polarizations and a large red shift in their z-polarizations upon crystallization from solution. Semiempirical ZINDO calculations provide a good model of the solid state, even with only a three-molecule segment, allowing reproduction of the red-shifting and intensity increase upon crystallization found experimentally. The modified nickel beta(s,p) bonding parameter of -5 found appropriate for Ni coordination in our previous studies of single Ni(CN)(4)(2-) planes and a helically stacked Cs(2)[Ni(CN)(4)].H(2)O crystal was changed to -3 for the more parallel-stacked Ni(CN)(4)(2-) planes in this case, while beta(d) was retained at -41. Crystal data are as follows: Na(2)[Ni(CN)(4)].3H(2)O, triclinic space group P1, a = 7.2980(10) A, b = 8.8620(10) A, c = 15.132(2) A, alpha = 89.311(5) degrees, beta = 87.326(5) degrees, gamma = 83.772(6) degrees, V = 971.8(2) A(3), T = 100 K, Z = 4, R = 0.024, R(w) = 0.064; Sr[Ni(CN)(4)].5H(2)O, monoclinic space group C2/m, a = 10.356(2) A, b = 15.272(3) A, c = 7.1331(10) A, beta = 98.548(12) degrees, V = 1115.6(3) A(3), T = 100 K, Z = 4, R = 0.024, R(w) = 0.059; Rb(2)[Ni(CN)(4)].1.05H(2)O, triclinic space group P1, a = 8.6020(10) A, b = 9.6930(10) A, c = 12.006(2) A, alpha = 92.621(6) degrees, beta = 94.263(6) degrees, gamma = 111.795(10) degrees, V = 924.0(2) A(3), T = 100 K, Z = 4, R = 0.034, R(w) = 0.067.     

Gas-liquid chromatography and mass spectrometry of methyl ethers of methyl N-acetyl-N-methyl-β-d-neuraminate methyl glycoside

Partial methylation of methyl N-acetyl-β-d-neuraminate methyl glycoside using methyl iodide and silver oxide gives a mixture of methyl ethers of methyl N-acetyl-N-methyl-β-d-neuraminate methyl glycoside, which was fractionated by chloroform-water partition followed by preparative column chromatography on silica gel. After trimethylsilylation of the fractions, gas-liquid chromatography on OV-101 and mass spectrometry facilitated the identification of 13 methyl ethers.