Reinvestigation of the stereochemistry of kulokekahilide-2

An attempt to carry out a total synthesis of kulokekahilide-2 (1) by macrolactonization of a seco acid prepared from a suitably protected hexapeptide and a dioxy acid moiety unexpectedly resulted in the formation of the 43-epimer (1a) of the cytotoxic depsipeptide, for which structure 1b has previously been proposed. A second attempt involving macrolactamization of the corresponding amino acid gave the target product, 1b, but the spectral data of the product did not match those of natural 1. Furthermore, neither 1a nor 1b showed any cytotoxicity, from which it is concluded that the structure of natural 1 is incorrect and should be re-examined.     

Nickel-catalyzed dimerization coupling reactions of vinyl Grignard reagents with 3, 4-membered cyclic ethers and chlorosilanes

Vinyl Grignard reagents reacted with cyclic ethers in the presence of a nickel catalyst giving rise to 2:1 coupling products 1 regioselectively. When chlorosilanes were used instead of cyclic ethers, 2:2 component coupling products 6 were obtained. A plausible reaction pathway via 1,3-butadiene-nickel complex and (2-butene-1,4-diyl)magnesium was proposed.     

Efficient synthesis of open-cage fullerene derivatives having 16-membered-ring orifices

The synthesis of 10 new open-cage fullerene derivatives with a 16-membered-ring orifice is being reported. These compounds, derived from the regioselective addition reaction of an aromatic hydrazine or hydrazone to isomeric diketone derivatives of C(60), were isolated in moderate to excellent yields.     

An orifice-size index for open-cage fullerenes

In the field of open-cage fullerenes, there was a lack of a universal standard that could correlate and quantify the orifice size of open-cage fullerenes. One cannot compare the relative orifice size by simple comparison of the number of atoms that composes the orifice. We present a general term for easy estimation of relative orifice size by defining an index for open-cage fullerenes. We estimated the corresponding effective areas A(area) for orifices of open-cage fullerenes by matching calculated activation energies Ea(calcd) for hydrogen release from open-cage fullerenes (B3LYP/6-31G**//B3LYP/3-21G) to the computed energies required for a hydrogen molecule passing through a cyclo[n]carbon ring. Then we define an index K(orifice) based on experimental hydrogen release rate, where K(orifice) = ln k/k degrees (k is rate constant of hydrogen-release rate of any open-cage fullerenes taken for comparison at 160 degrees C; k degrees is the hydrogen release rate from H2@4a taken as the standard compound). We synthesized several open-cage fullerenes and studied kinetics of a set of H2-encapsulated open-cage fullerenes to evaluate their K values. A correlation of the index K(orifice) with the effective areas A(area) showed a good linear fit (r2 = 0.972) that demonstrated a good interplay between experiment and theory. This allows one to estimate K(orifice) index and/or relative rate k of hydrogen release through computing activation energy Ea(calcd) for a designed open-cage fullerene.     

In Vitro Analyses of Spinach-Derived Opioid Peptides,Rubiscolins: Receptor Selectivity and Intracellular Activities through G Protein- and β-Arrestin-Mediated Pathways

Activated opioid receptors transmit internal signals through two major pathways: the G-protein-mediated pathway, which exerts analgesia, and the β-arrestin-mediated pathway, which leads to unfavorable side effects. Hence, G-protein-biased opioid agonists are preferable as opioid analgesics. Rubiscolins, the spinach-derived naturally occurring opioid peptides, are selective δ opioid receptor agonists, and their p.o. administration exhibits antinociceptive effects. Although the potency and effect of rubiscolins as G-protein-biased molecules are partially confirmed, their in vitro profiles remain unclear. We, therefore, evaluated the properties of rubiscolins, in detail, through several analyses, including the CellKey^TM assay, cADDis^® cAMP assay, and PathHunter^® β-arrestin recruitment assay, using cells stably expressing µ, δ, κ, or µ/δ heteromer opioid receptors. In the CellKey^TM assay, rubiscolins showed selective agonistic effects for δ opioid receptor and little agonistic or antagonistic effects for µ and κ opioid receptors. Furthermore, rubiscolins were found to be G-protein-biased δ opioid receptor agonists based on the results obtained in cADDis^® cAMP and PathHunter^® β-arrestin recruitment assays. Finally, we found, for the first time, that they are also partially agonistic for the µ/δ dimers. In conclusion, rubiscolins could serve as attractive seeds, as δ opioid receptor-specific agonists, for the development of novel opioid analgesics with reduced side effects.     

Self-organized monolayer assemblies of octopusporphyrins: photoinduced electron transfer and O 2 coordination in aqueous media

Bolaamphiphilic tetraresorcinolporphyrins with eight long side chains (octopusporphyrins) and their metal complexes form monolayered assemblies in bulk aqueous solution. The nano-structure, the photoinduced electron transfers and the O₂ coordination of these octopusporphyrin assemblies are described. In the micellar fibers of 1a and 1b, a unique spherical arrangement of eight methyl groups on both sides of the porphyrin ring plane provides hydrophobic porphyrin centers which align in a string of pearls. Exciton calculations indicated a tilt stacking porphyrins arrangement with a separation of 11 Å. These fibers fluoresced strongly; electron transfer reaction was therefore observed between the porphyrin center and hydrophobic quenchers as well as hydrophilic quenchers. The fibers were also active as photocatalysts in the reduction of dimethylviologen by triethanolamine. Octopusporphyrins with different metal centers can also produce fibrous aggregates, for example, H₂P/Zn(II)P and Zn(II)P/Fe(III)P couples. The fluorescence quenching of Zn(II)P in the Zn(II)P/Fe(III)P hybrid fibers can be ascribed to the intermolecular electron transfer within the fibers. In H₂P/Zn(II)P couple, excitation energy transfer from excited Zn¹*P to H₂P occurred after photoexcitation. Octopusporphyrin with four dialkylglycerophosphocholine groups on both sides of the ring plane ( 2b ) forms spherical unilamellar vesicles. Based on cryomicroscopy, a white line was observed with a diameter of 15 Å in the middle of the membrane which are obviously a porphyrin layer with low molecular packing. The octopusheme ( 2c ) vesicles prepared in a similar manner with 20-fold excess molar coexistence of 1-dodecyl-2-methylimidazole (DMIm) can bind and release oxygen reversibly at 25°C. Moreover, water-soluble octopusporphyrin ( 3a ) produced fluorescent and non-fluorescent monolayer assemblies by anion exchange of the head groups, e.g. 3a with sodium perchlorate showed planar sheets. An exciton calculation is consistent with a two-dimensional arrangement with porphyrin separations of 25.6 and 17.4 Å in the x- and y-directions, respectively. External addition of negatively charged electron acceptors, naphtoquinone sulfonate and anthraquinone sulfonate, led to partial quenching of the fluorescence of the central porphyrin layer. The results have been evaluated using equations derived for this special quenching. © 1998 John Wiley & Sons, Ltd.     

Novel Asymmetric and Stereospecific Aziridination of Alkenes with a Chiral Nitridomanganese Complex

The addition of pyridine N -oxide is necessary to obtain high enantioselectivities in the asymmetric aziridination of styrene derivatives through transfer of a nitrogen atom from chiral, toluenesulfonic anhydride activated nitridomanganese complex 1 [Eq. (a)]. Remarkably, high stereospecificity was observed in all the aziridinations of trans- and cis-1,2-disubstituted alkenes. R¹=H, Me, nPr, iPr; R²=H, Me; Ts=p-toluenesulfonyl.     

FTIR spectroscopic study on crystallization process of poly(ethylene-2,6-naphthalate)

In situ Fourier transform infrared (FTIR) measurements were carried out to elucidate conformation changes occurring during the isothermal melt crystallization of poly(ethylene-2,6-naphthalate) (PEN). Based on the band assignments for the components of the amorphous, α-crystal form, and β-crystal form of PEN in film samples, the in situ data was analyzed in terms of the amorphous- and crystal-trans conformations. It was observed at a higher isothermal crystallization temperature that the formation of amorphous-trans conformations precedes the growth of crystals. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35: 2741–2747, 1997