Sterically Congested Phosphite Ligands: Synthesis,crystallographic characterization,and observation of unprecedented eight-Bond 31P,31P coupling in the 31P-NMR spectra

The synthesis and characterization of 2-{1-{3,5-bis(1,1-dimethylethyl)-2-{[2,4,8,10-tetrakis(1,1-dimethylethyl)dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl]oxy}phenyl}ethyl}-4,6-bis(1,1-dimethylethyl)phenyl diphenyl phosphite ( 6 ) is described. In the ³¹P-NMR spectrum (¹H-decoupled) of 6 , an unprecedented eight-bond P,P coupling of J = 72.8 Hz is observed. In the X-ray crystal structure of 6 , an intramolecular P–P distance of 3.67 Å is found, which is within the sum of the van-der-Waals radii of the P-atoms. The observed intramolecular P–P distance suggests that a through-space coupling mechanism is operative. The solid-state conformation of 6 is compared to the conformation obtained by semi-empirical MO geometry optimizations (PM3 method). The calculated geometry suggests that the solid-state structure is near a true energy minimum, but that crystal-packing forces decrease the intramolecular P–P distance in the solid state. In the absence of crystal-packing forces, however, the collisional and vibrational energy available in solution may lead to the population of states with a shortened intramolecular P–P distance in 6 . The proximity of the P-atoms in 6 is due to restricted conformational freedom resulting from steric congestion within the molecule. The free energy of activation (ΔG* = 10.2 and 10.8 kcal/mol for unequal populations of exchanging conformers) for ring inversion of the dibenzo[d,f][1,3,2]dioxaphosphepin ring in 6 is determined by variable-temperature ³¹P-NMR spectroscopy. Semi-empirical MO calculation on model compounds suggest that the structure of the transition state for ring inversion has the two aryl rings and O-atoms in a common plane, with the P-atom lying above this plane.     

Discriminating the helical forms of peptides by NMR and molecular dynamics simulation

The HNCO NMR pulse sequence was applied to three selectively labeled (15)N and (13)C isotopic homologues of the peptide Ac-WAAAH(AAARA)(3)A-NH(2) to probe directly for hydrogen bonds between residues 8 and 11 (characteristic of a 3(10)-helix), 8 and 12 (alpha-helix), and 8 and 13 (pi-helix). The experiments demonstrate conclusively, and in agreement with circular dichroism studies, that the center of the peptide is alpha-helical; there is no discernible 3(10)- or pi-helix at these specific positions. Molecular dynamics simulations of the preceding peptide and Ac-(AAAAK)(3)A-NH(2) in water using the potential energy parameter set CHARMM22/CMAP correctly yield an alpha-helix, in contrast to simulations with the set CHARMM22, which result in a pi-helix.     

Calculation of the electronic properties of neutral and ionized divalent-metal clusters

The electronic properties of neutral and ionized divalent-metal clusters have been studied using a microscopic theory, which takes into account the interplay between van der Waals (vdW) and covalent bonding in the neutral clusters, and the competition between hole delocalization and polarization energy in the ionized clusters. By calculating the ground-state energies of neutral and ionized Hg _n clusters, we determine the size dependence of the bond character and the ionization potentialI _p (n). For neutral Hg _n clusters we obtain a transition from van der Waals to covalent behaviour at the critical sizen _c ～10–20 atoms. Results forI _p (Hg _n ) withn≤20 are in good agreement with experiments, and suggest that small Hg _n ⁺ clusters can be viewed as consisting of a positive trimer core Hg ₃ ⁺ surrounded byn?3 polarized neutral atoms.     

Synthesis of monobutyrylglycerol by transesterification with soluble and immobilized lipases

Transesterification between ethyl butyrate and glycerol using very different lipase preparations (native, modified, and immobilized) in a two-phase system—no extra solvent added—has been investigated. Optimal conversion was obtained with the presence of 5% water in the reaction mixture. Only monobutyrin was produced in all conditions tested. The best enzyme preparations were nativeCandida cylindracea lipase,Mucor miehei lipase immobilized on a phenol-formaldehyde exchange resin (Lipozyme?), andC. cylindracea lipase immobilized on Celite.     

Direct, two-step synthetic pathway to novel dibenzo[a,c]phenanthridines

Novel dibenzo[a,c]phenanthridines are prepared regioselectively by the application of a straightforward synthetic pathway, starting from new 3,4-diaryl- and 3,4-dihydro-3,4-diarylisoquinolines prepared via Ritter-type heterocyclization and the more classical two-step reductive amination/Bischler-Napieralski cyclization of triarylethanones, respectively. A comparative study of nonphenolic oxidative coupling methodologies provides a highly efficient procedure, based on the hypervalent iodine reagent phenyliodine(III) bis(trifluoroacetate) (PIFA), to accomplish the final coupling step.     

An advantageous route to oxcarbazepine (trileptal) based on palladium-catalyzed arylations free of transmetallating agents

[reaction: see text] A new route to oxcarbazepine (Trileptal), the most widely prescribed antiepileptic drug, starting from commercially available 2'-aminoacetophenone and 1,2-dibromobenzene, is reported. The sequentially accomplished key steps are palladium-catalyzed intermolecular alpha-arylation of ketone enolates and intramolecular N-arylation reactions. After several experiments to establish the best conditions for both arylation processes, the target oxcarbazepine is obtained in a satisfactory overall yield, minimizing the number of steps and employing scalable catalytic procedures developed in partially aqueous media.     

月光花素甲(Ⅰ)、(Ⅱ)整体分子结构的测定

本文对月光花素甲(Calonyctin A)的整体分子结构分析加以完善并进行总结。前文报道月光花素甲是两个分子量相差28a.m.u的糖甙类同系物分子的混合物。这两个分子(简称M_1和M_2)分别称为月光花素甲(Ⅰ)与月光花素甲(Ⅱ)(Calonyctm A_1,CalonyctinA_2),分子量分别为938与910。它们分别含