Asymmetric syntheses of fused bicyclic compounds by conjugate additions of allylic organolithium species to activated olefins and subsequent cyclizations

[reaction: see text]. Addition of the configurationally stable organolithium species produced by enantioselective deprotonation of N-Boc-N-(p-methoxyphenyl) allylamines to alpha,beta-unsaturated carbonyl compounds affords 1,4-addition products in good yields with high diastereomeric and enantiomeric ratios. Further transformations of these compounds provide [3.3.0]-, [4.3.0]-, [5.3.0]-, and [5.4.0]-carbocycles and heterocycles with high stereoselectivities.     

Simple syntheses, structural diversity, and Tishchenko reaction catalysis of neutral homoleptic rare earth(II or III) 3,5-di-tert-butylpyrazolates--the structures of

The homoleptic rare-earth pyrazolate complexes [Sc(tBu2pz)3], [Ln2(tBu2pz)6] (Ln = La, Nd, Sm, Lu), [Eu4(tBu2pz)8] and the mixed oxidation state species [Yb2(tBu2pz)5] (tBu2pz = 3,5-di-tert-butylpyrazolate) have been prepared by a simple reaction between the corresponding rare-earth metal and 3,5-di-tert-butylpyrazole, in the presence of mercury, at elevated temperatures. In addition, [Yb2(tBu2pz)6] was prepared by redox transmetallation/ligand exchange between ytterbium, diphenylmercury(II) and tBu2pzH in toluene, whilst the same reactants in toluene under different conditions or in diethyl ether gave [Yb2(tBu2pz)5]. The complexes of the trivalent lanthanoids display dimeric structures [Ln2(tBu2pz)6] (Ln = La, Nd, Yb, Lu) with chelating eta2-terminal and eta2:eta2-bridging pyrazolate coordination. The considerably smaller Sc3+ ion forms monomeric [Sc(tBu2pz)3] of putative D3h molecular symmetry, with pyrazolate ligands solely eta2-bonded. [Eu4(tBu2pz)8] is a structurally remarkable tetranuclear EuII complex with two types of europium centres in a linear array. The outer two are bonded to one terminal and two bridging pyrazolates, and the inner two are coordinated by four bridging ligands. Unprecedented mu-eta5:eta2 pyrazolate ligation is observed, with each outer Eu2+ sandwiched between two eta5-bonded pyrazolate groups, which are also eta2-linked to an inner Eu2+. The two inner Eu2+ ions are linked together by two equally occupied components of each of two symmetry related, disordered pyrazolate groups with one component eta4:eta2 bridging and one eta3:eta2 bridging. [La2(tBu2pz)6] has also been shown to be a Tishchenko reaction catalyst with several organic substrates.     

An analysis of the interactions between the Sem-5 SH3 domain and its ligands using molecular dynamics, free energy calculations, and sequence analysis.

The Src-homology-3 (SH3) domain of the Caenorhabditis elegans protein Sem-5 binds proline-rich sequences. It is reported that the SH3 domains broadly accept amide N-substituted residues instead of only recognizing prolines on the basis of side chain shape or rigidity. We have studied the interactions between Sem-5 and its ligands using molecular dynamics (MD), free energy calculations, and sequence analysis. Relative binding free energies, estimated by a method called MM/PBSA, between different substitutions at sites -1, 0, and +2 of the peptide are consistent with the experimental data. A new method to calculate atomic partial charges, AM1-BCC method, is also used in the binding free energy calculations for different N-substitutions at site -1. The results are very similar to those obtained from widely used RESP charges in the AMBER force field. AM1-BCC charges can be calculated more rapidly for any organic molecule than can the RESP charges. Therefore, their use can enable a broader and more efficient application of the MM/PBSA method in drug design. Examination of each component of the free energy leads to the construction of van der Waals interaction energy profiles for each ligand as well as for wild-type and mutant Sem-5 proteins. The profiles and free energy calculations indicate that the van der Waals interactions between the ligands and the receptor determine whether an N- or a Calpha-substituted residue is favored at each site. A VC value (defined as a product of the conservation percentage of each residue and its van der Waals interaction energy with the ligand) is used to identify several residues on the receptor that are critical for specificity and binding affinity. This VC value may have a potential use in identifying crucial residues for any ligand-protein or protein-protein system. Mutations at two of those crucial residues, N190 and N206, are examined. One mutation, N190I, is predicted to reduce the selectivity of the N-substituted residue at site -1 of the ligand and is shown to bind similarly with N- and Calpha-substituted residues at that site.     

Binding of methyl orange and its homologs by powdered nylon 612: Peculiar temperature dependence on the binding

The ability of powdered Nylon 612 to bind methyl orange, ethyl orange, propyl orange, and butyl orange was investigated at 5, 15, 25 and 35°C in an aqueous solution. The amount of binding of the dye is much higher with this polyamide than with powdered Nylon 66 reported previously,¹ although the former polymer has fewer amide end groups. The Van't Hoff plots of the first binding constant for the binding of butyl orange and propyl orange by powdered Nylon 612 exhibit a bell-shaped curve, whereas the plots for methyl orange and ethyl orange do not. Maximal binding occurs at approximately 15°C for propyl orange and at about 25°C for butyl orange. This is the first instance where the peculiar temperature dependence of the binding constant has been found in the binding of propyl orange, whose hydrophobicity is less than that of butyl orange. These tendencies can be accounted for in terms of increased hydrophobic of butyl orange. These tendencies can be accounted for in terms of increased hydrophobic domains in powdered Nylon 612 and enhanced hydrophobic contributions in the binding process.     

Biomimetic oxidative transformations of pericine: partial synthesis of apparicine and valparicine, a new pentacyclic indole alkaloid from Kopsia

A new pentacyclic indole alkaloid of the pericine-type, valparicine, representing the first member of this sub-group, was obtained from a Malayan Kopsia species and the structure was established by spectroscopic analysis. A partial synthesis of valparicine and apparicine from pericine was carried out via the Potier-Polonovski reaction and the biogenetic implications are discussed.