Malliavin differentiability of solutions of rough differential equations

In this paper we study rough differential equations driven by Gaussian rough paths from the viewpoint of Malliavin calculus. Under mild assumptions on coefficient vector fields and underlying Gaussian processes, we prove that solutions at a fixed time are smooth in the sense of Malliavin calculus. Examples of Gaussian processes include fractional Brownian motion with Hurst parameter larger than 1/4.     

Direct Nucleophilic Addition to N‐Alkoxyamides

While the synthesis of amide bonds is now one of the most reliable organic reactions, functionalization of amide carbonyl groups has been a long‐standing issue due to their high stability. As an ongoing program aimed at practical transformation of amides, we developed a direct nucleophilic addition to N‐alkoxyamides to access multisubstituted amines. The reaction enabled installation of two different functional groups to amide carbonyl groups in one pot. The N‐alkoxy group played important roles in this reaction. First, it removed the requirement for an extra preactivation step prior to nucleophilic addition to activate inert amide carbonyl groups. Second, the N‐alkoxy group formed a five‐membered chelated complex after the first nucleophilic addition, resulting in suppression of an extra addition of the first nucleophile. While diisobutylaluminum hydride (DIBAL‐H) and organolithium reagents were suitable as the first nucleophile, allylation, cyanation, and vinylation were possible in the second addition including inter‐ and intramolecular reactions. The yields were generally high, even in the synthesis of sterically hindered α‐trisubstituted amines. The reaction exhibited wide substrate scope, including acyclic amides, five‐ and six‐membered lactams, and macrolactams.     

Advances in Artificial Cell Membrane Systems as a Platform for Reconstituting Ion Channels

An artificial cell membrane that is composed of bilayer lipid membranes (BLMs) with transmembrane proteins incorporated within them represents a well‐defined system for the analysis of membrane proteins, especially ion channel proteins that are major targets for drug design. Because the BLM system has a high compatibility with recently developed cell‐free expression systems, it has attracted attention as a next‐generation drug screening system. However, three issues associated with BLM systems, i. e., their instability, the need for non‐volatile organic solvents and a low efficiency of ion channel incorporation, have limited their use as a drug screening platform. In this personal account, we discuss our recent approaches to address these issues based on microfabrication. We also discuss the potential for using the BLM system combined with cell‐free expression systems as a drug screening system for future personalized medicine.     

Behavior of bound water in polyethylene oxide studied by DSC and high-frequency spectroscopy.

Measurements of DSC, NMR and high-frequency spectroscopy have been done on PEO-H2O and PEO-H2O-HQ mixed systems. DSC measurements show that water molecules contained in PEO are divided roughly into two species: freezable water and non-freezable water. By 1H-NMR measurements, PEO and H2O protons show an absorption peak around 3.6 ppm and 4.5 ppm, respectively. All the PEO-H2O samples containing H2O show NMR absorption signals, suggesting the existence of movable H2O. Samples with H2O molar ratio over 0.5, show one absorption peak of H2O protons, and more than two peaks of PEO. The results from DSC and NMR measurements show that the bound state of H2O in PEO, as well as the mobility of PEO itself, varies according to the water content in PEO-H2O samples. On the other hand, DSC measurements give the result that PEO-H2O-HQ systems can be considered as homogeneous so long as the content of H2O and/or HQ is not so high. Furthermore, the water molecules in the system exist as bound water. Results of high-frequency spectroscopic measurements for the PEO-H2O and PEO-H2O-HQ systems show good agreement with those of DSC and NMR measurements.     

Newly developed chemical probes and nano-devices for cellular analysis.

A cellular analyzing system including a "real-time cellular imaging system" and a "comprehensive analyzing system for cellular responses" was developed. A "real-time cellular imaging system" is a system used to measure real-time imaging of multiple phenomena of a single cell with high special and temporal resolutions for the purpose to understand the pathology and physiology in a single cell and realize to single cell level diagnosis. A "real-time cellular imaging system" includes multi-probe imaging with AFM (atomic force microscopy), optical and SECM (scanning electrochemical microscopy) modes, which provides us with topological information and biochemical reactions at the local area of the interior and exterior of a cell. Scanning electrochemical/optical microscopy was applied to image PC12 cells. On the other hand, cells respond to their specific substances via their ligands. Therefore, the comprehensive analysis of protein-protein interaction is the important issue to determine the functions of cells. For this purpose, a "comprehensive analysis system for cellular responses" was developed. This system is based on SPR (surface plasmon resonance) and MS (mass spectrometry) using a nano-fabricated substrate. The interaction between IL-1 beta and anti-IL-1 beta antibodies was detected.     

Nagelamides K and L, dimeric bromopyrrole alkaloids from sponge Agelas species

Two new dimeric bromopyrrole alkaloids, nagelamides K (1) and L (2), have been isolated from Okinawan marine sponges Agelas species, and the structures and stereochemistry were elucidated from spectroscopic data. Nagelamide K (1) is a bromopyrrole alkaloid possessing a rare piperidinoiminoimidazolone ring with an aminoimidazole ring and a taurine unit, while nagelamide L (2) is a unique dimeric bromopyrrole alkaloid containing an ester linkage. Nagelamides K (1) and L (2) exhibited antimicrobial activity.     

Hyrtioseragamines A and B, new alkaloids from the sponge Hyrtios species

Two novel alkaloids with a furo[2,3-b]pyrazin-2(1H)-one moiety and a guanidino group, hyrtioseragamines A (1) and B (2), have been isolated from an Okinawan marine sponge Hyrtios species. The structures of 1 and 2 were elucidated on the basis of spectroscopic data and chemical conversions. Compounds 1 and 2 are the first natural products possessing a furo[2,3-b]pyrazine-related moiety.     

Isolation,synthesis, and biological activity of biphenyl and m-terphenyl-type compounds from Dictyostelium cellular slime molds

From the fruiting bodies of Dictyostelium polycephalum, we obtained four aromatic compounds: dictyobiphenyl A (1) and B (2) and dictyoterphenyl A (3) and B (4). The synthesis of 1–4 was performed to confirm the structures and obtain sufficient material for biological evaluation. Compound 3 was the first example of nitrogen-containing natural m-terphenyls, and the isolation of novel classes of compounds such as 3 shows that cellular slime molds are promising sources in natural product chemistry. Moreover, dictyoterphenyl A (3) showed cancer cell-selective antiproliferative activity (IC₅₀ 2.3–8.6 μM).