2,2′-Isopropylidenebis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline] ligand for asymmetric cyclization-carbonylation of meso-2-alkyl-2-propargylcyclohexane-1,3-diols

The oxidative cyclization-carbonylation of meso-2-alkyl-2-propargylcyclohexane-1,3-diols mediated by Pd(II) with chiral bisoxazoline (box ligand) afforded bicyclic-β-alkoxyacrylates. Based on a ligand screening, 2,2′-isopropylidenebis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline] ligand has been developed. The products with a chiral quaternary carbon were obtained in 71-100% yields with 85-95% ee.     

Synthetic studies directed toward the assembly of the C-glycoside fragment of the telomerase inhibitor D8646-2-6

[reaction: see text] Construction and characterization of the C-glycosidic moiety of telomerase inhibitor D8646-2-6 (1) are described. This is the first example of the C-glycosylation using electron-poor aromatics, 4-hydroxypyrone, as a glycosyl acceptor. The glycosylation reaction and base-promoted isomerization affords desired beta-C-glycoside in a 61% overall yield.     

The first synthesis of a methano[60]fullerene with an electron-donating group at the methano-bridge carbon: synthesis and reaction of aminomethano[60]fullerene

[reaction: see text] Aminomethano[60]fullerene was synthesized for the first time as a trifluoromethanesulfonic acid salt by applying the Curtius rearrangement of azidocarbonylmethano[60]fullerene as the key reaction. Aminomethano[60]fullerene thus obtained was found to be able to react with various acyl chlorides to afford the corresponding amides.     

Structure and ethanol complexation of cyclic tetrasaccharide in aqueous solution studied by NMR and molecular mechanics

The structure and ethanol complexation of a cyclic tetrasaccharide (CTS) in aqueous solution were investigated by proton NMR spectroscopy and molecular mechanics calculations. Two glucose units, A and B, of CTS are alternatively bonded by alpha-1,3 and alpha-1,6 linkages. The overlapped signals of protons A5, A6S, A6R, B3, B6S and B6R were resolved by spectral simulations to determine their chemical shifts and vicinal coupling constants. All vicinal coupling constants except for the A5-A6 spin system are consistent with the dihedral angles in the X-ray crystal structure. Each of protons A5, A6S, and A6R in the two units of A is equivalent with respect to the chemical shift. The vicinal coupling constants of (3)J(5-6S) and (3)J(5-6R) for unit A are close to the average of two rotamers that are present in crystals. The intensities of cross-peaks in the rotating frame nuclear Overhauser effect spectroscopy (ROESY) spectrum were rather well correlated with the effective distances calculated for the X-ray structure and molecular mechanics structures calculated in vacuo and water, although they are slightly better correlated with molecular mechanics structure in vacuo than with the other structures. From the changes of the chemical shifts of several CTS protons with increasing ethanol concentration, it was suggested that adsorption sites of ethanol on the plate structure of CTS are protons B2 and B4 (site B) in the concave face side and protons A1 and A2 (site A) in the convex back side. The binding constants for sites A and B are 0.0061 and 0.0176 M(-1), respectively. These binding constants are much smaller than a value of 4.1 M(-1) for the ethanol-alpha-cyclodextrin complex.     

Ring‐Opening Reactions of 3‐Aryl‐1‐benzylaziridine‐2‐carboxylates and Application to the Asymmetric Synthesis of an Amphetamine‐Type Compound

Nucleophilic ring‐opening reactions of 3‐aryl‐1‐benzylaziridine‐2‐carboxylates were examined by using O‐nucleophiles and aromatic C‐nucleophiles. The stereospecificity was found to depend on substrates and conditions used. Configuration inversion at C(3) was observed with O‐nucleophiles as a major reaction path in the ring‐opening reactions of aziridines carrying an electron‐poor aromatic moiety, whereas mixtures containing preferentially the syn‐diastereoisomer were generally obtained when electron‐rich aziridines were used (Tables 1–3). In the reactions of electron‐rich aziridines with C‐nucleophiles, S_N2 reactions yielding anti‐type products were observed (Table 4). Reductive ring‐opening reaction by catalytic hydrogenation of (+)‐trans‐(2S,3R)‐3‐(1,3‐benzodioxol‐5‐yl)aziridine‐2‐carboxylate (+)‐trans‐ 3c afforded the corresponding α‐amino acid derivative, which was smoothly transformed into (+)‐tert‐butyl [(1R)‐2‐(1,3‐benzodioxol‐5‐yl)‐1‐methylethyl]carbamate((+)‐ 14 ) with high retention of optical purity (Scheme 6).     

Structural disorder in Ba0.6Sr0.4Al2O4

The structural disorder in Ba_0.6Sr_0.4Al₂O₄ (space group P6₃22) was investigated by X-ray powder diffraction and selected-area electron diffraction (SAED). The initial structural model was determined using direct methods, and it was further modified by the combined use of Rietveld method and maximum-entropy method (MEM). MEM-based pattern fitting method was subsequently applied, resulting in the final reliability indices of R_wp=9.61%, R_p=6.96%, R_B=1.40% and S=1.25. The electron density distribution was satisfactorily expressed by the split-atom model in which the strontium/barium and oxygen atoms were split to occupy the lower symmetry sites. The diffuse scattering in SAED was mainly attributable to the positional disorder of oxygen atoms.     

Facile peptide thioester synthesis via solution-phase tosylamide preparation

Preparation of peptide thioester is essential for native chemical ligation and block condensation. Our novel methodology involves conversion of the carboxylic acid of a peptide into a thioester using p-toluenesulfonyl isocyanate, followed by alkylation, then thiol substitution. Our methodology can also be used for the preparation of glycopeptide thioesters. Furthermore, it is possible to carry out the reaction as a sequential peptide chemical ligation.     

Polyether-bridged sexithiophene as a complexation-gated molecular wire for intramolecular photoinduced electron transfer

The porphyrin-sexithiophene-fullerene triad 2, where the two central thiophene units of the sexithiophene spacer are bridged with a crown-ether-like polyether chain, undergoes efficient intramolecular electron transfer from the photoexcited porphyrin moiety to the fullerene through the sexithiophene. However, complexation with a sodium cation in the crown ether ring causes complete suppression of electron transfer as a result of a drastic conformational change of the sexithiophene backbone. Furthermore, decomplexation resumes the photoinduced electron transfer. This on/off switching phenomenon indicates that the polyether-bridged sexithiophene can function as a complexation-gated molecular wire.     

Structural regulation of a peptide-conjugated graft copolymer: a simple model for amyloid formation

The self-assembly of peptides and proteins into beta-sheet-rich high-order structures has attracted much attention as a result of the characteristic nanostructure of these assemblies and because of their association with neurodegenerative diseases. Here we report the structural and conformational properties of a peptide-conjugated graft copolymer, poly(gamma-methyl-L-glutamate) grafted polyallylamine (1) in a water-2,2,2-trifluoroethanol solution as a simple model for amyloid formation. Atomic force microscopy revealed that the globular peptide 1 self-assembles into nonbranching fibrils that are about 4 nm in height under certain conditions. These fibrils are rich in beta-sheets and, similar to authentic amyloid fibrils, bind the amyloidophilic dye Congo red. The secondary and quaternary structures of the peptide 1 can be controlled by manipulating the pH, solution composition, and salt concentration; this indicates that the three-dimensional packing arrangement of peptide chains is the key factor for such fibril formation. Furthermore, the addition of carboxylic acid-terminated poly(ethylene glycol), which interacts with both of amino groups of 1 and hydrophobic PMLG chains, was found to obviously inhibit the alpha-to-beta structural transition for non-assembled peptide 1 and to partially cause a beta-to-alpha structural transition against the 1-assembly in the beta-sheet form. These findings demonstrate that the amyloid fibril formation is not restricted to specific protein sequences but rather is a generic property of peptides. The ability to control the assembled structure of the peptide should provide useful information not only for understanding the amyloid fibril formation, but also for developing novel peptide-based material with well-defined nanostructures.