Total Synthesis of the 7,10‐Epimer of the Proposed Structure of Amphidinolide N,Part II: Synthesis of C17–C29 Subunit and Completion of the Synthesis

The total synthesis of 7,10‐epimer of the proposed structure of amphidinolide N was accomplished. The requisite chiral C17–C29 subunit was assembled stereoselectively via Keck allylation, Shi epoxidation, diastereoselective 1,3‐reduction, and a later oxidative synthesis of the THF framework. The C1–C13 and C17–C29 subunits were successfully coupled using a Enders RAMP “linchpin” as the C14–C16 three carbon unit, thereby controlling the chirality at C14 and C16. The labile allyl epoxy moiety was successfully constructed by Grieco–Nishizawa olefination at a final stage of the synthesis.     

Comparative investigation of Au nano-particle formation process dependent upon various protective agents

Formation process of gold nanoparticles was investigated by near-field heterodyne transient grating method. In the absence of the protective agents, although the diffusion of H[Au^ICl₂] could be observed after the photo-reduction of H[Au^IIICl₄], the diffusion of nanoparticle-seeds was not observed. On the other hand, in the presence of the protective agents, the diffusion of a complex molecule (Au and protective agent) and nanoparticle-seeds could be observed. From these results, it was found that enough amount of the complex is essential for the nanoparticle formation. We also investigated the formation process with four different chemicals as a protective agent. The hydrodynamic radius of nanoparticle-seeds generated in the poly(vinyl pyrrolidone) and TritonX-100 solutions were larger than those generated in the Tween 20 and Brij 58 solutions. The former two have hydrophilic chain in the molecular structure; on the other hand, the latter two have hydrophobic alkyl chain. Based on those facts, we concluded that the interaction between the chains of the complex molecule plays an important role in the nanoparticle formation process.     

Synthesis and Cytotoxic Activity of Oxidized Galactomannan/ADR Conjugate

Abstract

Many polysaccharides are expected to apply as biomaterials because they generally show good biocompatibilities and biodegradabilities. It has recently been reported that the saccharides play important roles in biological recognition and the transmission of biological information on a cellar surface. Galactomannan (GalM) is a polysaccharide whose main chain is composed of β-1,4-linked mannose units only. It has some branching α-galactose residues at the C-6 position of mannose units. Therefore, it was of interest of us to use GalM as a drug carrier which was targeted to hepatocyte having a galactose receptor on its cellar surface. Dicarboxy-galactomannan (DC-GalM), which has reactive functional groups and is a carboxylic acid derivative of galactomannan, was prepared by IO^4-/CIO^2- oxidation of GalM. The obtained DC-GalM showed specific binding with maclura pomifera (MPA) [1] which has a specificity to α-galactose. Moreover, DC-GalM showed selective incorporation into hepatocyte. Adriamycine (ADR), which is one of the most prominent anticancer agents, was immobilized to DC-GalM. The DC-GalM/ADR conjugate showed specific cytotoxic activity against HepG2 human hepatoma cells which have a galactose receptor on the cell surface, compared with Hela utrocervical carcinoma cells which have no galactose receptor.     

Synthesis of Substituted Phenyl Esters of Amino Acids and Polycondensation in Langmuirblodgett Films

Long-alkyl-chain phenyl esters of β-alanine, glycine, and L-valine were prepared, and their monolayer properties were correlated with their molecular structures. These compounds formed stable monolayers on acidic subphases. In particular, the p-hexadecylphenyl esters of β-alanine and glycine were remarkably stable, and their monolayers could be deposited on calcium fluoride plates as Y-type film by Blodgett's technique. The polycondensation of multilayers under an atmosphere saturated with triethylamine was investigated by changes in the IR spectra. It was determined that the polycondensation proceeded by a first-order reaction mechanism in the initial stage and that the rate in multilayers was faster than that in the bulk crystalline powder. These results suggest that the polycondensation is accelerated by a regular arrangement of the monomer in the multilayers, where the active sites are concentrated and located better for the polycondensation. In the case of the polycondensation in multilayers of the glycine ester, two kinds of condensation proceeded to afford poly(glycine) and 2,5-piperazinedione.     

Discovery of Oxysterol-Derived Pharmacological Chaperones for NPC1: Implication for the Existence of Second Sterol-Binding Site

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Highlights? Niemann-Pick disease type C is caused by folding defect in NPC1 protein ? Oxysterols and chemically optimized derivatives act as pharmacological chaperones ? Defects in localization, stability, maturation, and function were corrected in cell ? These derivatives bind to second sterol-binding site on NPC1 protein     

Influence of the Metal Ion on the Two‐Photon Absorption Properties of Lanthanide Complexes Including Near‐IR Emitters

The synthesis of tris(2‐thenoyltrifluoroacetonate)lanthanide(III) complexes featuring a diethylaminostyryl‐2,2′‐bipyridine coligand was achieved for lanthanum; the near‐infrared (NIR) emitters neodymium, erbium, and ytterbium; and the transition‐metal yttrium. The photophysical properties were thoroughly studied, and it was demonstrated that the conjugated bipyridine ligand acts as a good antenna for the sensitization of the NIR emitters. The two‐photon absorption (TPA) properties of all five complexes were investigated by using both two‐photon excited fluorescence and the Z‐scan method. We demonstrate that the nature of the rare earth ion has almost no influence on the TPA properties centered on the conjugated bipyridyl ligand. Finally, we show that Yb^III is sensitized by a two‐photon antenna effect, and that Nd^III is mostly sensitized by a one‐photon process involving direct excitation of forbidden f–f transitions.     

Osmium(III) and Osmium(V) Complexes Bearing a Macrocyclic Ligand: A Simple and Efficient Catalytic System for cis‐Dihydroxylation of Alkenes with Hydrogen Peroxide

A simple protocol that uses [Os^III(OH)(H₂O)(L ‐N₄Me₂)](PF₆)₂ ( 1 ; L ‐N₄Me₂=N,N′‐dimethyl‐2,11‐diaza[3.3](2,6)pyridinophane) as a catalyst and H₂O₂ as a terminal oxidant for efficient cis‐1,2‐dihydroxylation of alkenes is presented. Unfunctionalized (or aliphatic) alkenes and alkenes/styrenes containing electron‐withdrawing groups are selectively oxidized to the corresponding vicinal diols in good to excellent yields (46–99 %). In the catalytic reactions, the stoichiometry of alkene:H₂O₂ is 1:1, and thus the oxidant efficiency is very high. For the dihydroxylation of cyclohexene, the catalytic amount of 1 can be reduced to 0.01 mol % to achieve a very high turnover number of 5500. The active oxidant is identified as the Os^V(O)(OH) species ( 2 ), which is formed via the hydroperoxide adduct, an Os^III(OOH) species. The active oxidant 2 is successfully isolated and crystallographically characterized.     

Synthesis of Optically Active Aromatic Ether Ketone Macrocycles Containing 2,2′-Dimethoxy-1,1′-binaphthyl-6,6′-diyl Moieties

Optically active aromatic ether ketone macrocycles containing 2,2′-dimethoxy-1,1′-binaphthyl-6,6′-diyl moieties were synthesized through electrophilic aromatic substitution reaction and stepwise nucleophilic aromatic substitution reactions. Structures of the resulting macrocycles were confirmed by NMR and matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass measurements.