Fabrication of microfluidic optical waveguides on glass chips with femtosecond laser pulses

We describe the fabrication of microfluidic channel structures on the surface of a borosilicate glass slide by femtosecond laser direct writing for optical waveguide application. Liquid with a variable refractive index is fed into the microchannel, serving as the core of the waveguide. We demonstrate that either a multimode or a single-mode waveguide can be achieved by controlling the refractive index of the liquid.     

Asymmetric Total Synthesis of ent‐Pyripyropene A

An asymmetric total synthesis of ent‐pyripyropene A was achieved by a convergent synthetic route. We used our originally developed Ti^III‐catalyzed radical cyclization to construct an AB‐ring portion that consisted of a trans‐decalin skeleton with five contiguous stereogenic centers. The coupling between the AB‐ring and the DE‐ring portions, and a subsequent C‐ring cyclization, led to the total synthesis of ent‐pyripyropene A. An evaluation of the insecticidal activity of ent‐pyripyropene A against two aphid species revealed that ent‐pyripyropene A was 35–175 times less active than naturally occurring pyripyropene A. This result indicated that the biological target of pyripyropene A recognizes the absolute configuration of pyripyropene A.     

Solid‐Phase Combinatorial Synthesis and Biological Evaluation of Destruxin E Analogues

The solid‐phase combinatorial synthesis of cyclodepsipeptide destruxin E has been demonstrated. The combinatorial synthesis of cyclization precursors 8 was achieved by using a split and pool method on SynPhase Lanterns. The products were successfully macrolactonized in parallel in the solution phase by using 2‐methyl‐6‐nitrobenzoic anhydride and 4‐(dimethylamino)pyridine N‐oxide to afford macrolactones 9 , and the subsequent formation of an epoxide in the side chain gave 18 member destruxin E analogues 6 . Biological evaluation of analogues 6 indicated that the N‐MeAla residue was crucial to the induction of morphological changes in osteoclast‐like multinuclear cells (OCLs). Based on structure–activity relationships, azido‐containing analogues 15 were then designed for use as a molecular probe. The synthesis and biological evaluation of analogues 15 revealed that 15 b , in which the Ile residue was replaced with a Lys(N₃) residue, induced morphological changes in OCLs at a sufficient concentration, and modification around the Ile residue would be tolerated for attachment of a chemical tag toward the target identification of destruxin E ( 1 ).     

Mapping of the primary mannose binding site of pradimicin A

Pradimicin A (PRM-A) is an actinomycete-derived antibiotic with the lectin-like property of being able to recognize D-mannopyranoside (Man) in the presence of Ca(2+) ion. PRM-A and its derivatives have been attracting a great deal of attention as the only family of natural carbohydrate receptors with nonpeptidic skeleton and, more recently, as conceptually novel drug candidates for human immunodeficiency virus (HIV). Despite its scientific interest and potential therapeutic importance, understanding how PRM-A recognizes Man has been severely limited. Conventional interaction analysis of PRM-A with Man in solution has been frustrated by aggregation of PRM-A and the three-component equilibrium consisting of the [PRM-A(2)/Ca(2+)], [PRM-A(2)/Ca(2+)/Man(2)], [PRM-A(2)/Ca(2+)/Man(4)] complexes, and their mixed oligomers. In this Article, we demonstrate the interaction analysis of PRM-A with methyl α-D-mannopyranoside (Man-OMe) in the solid state, which benefits from aggregate-forming propensity of PRM-A and eliminates the problem associated with the complicated equilibrium in solution. Isothermal titration calorimetry (ITC) analysis and coprecipitation experiments revealed that the primary Man binding of PRM-A is markedly tighter than the secondary one, leading to preparation of the solid aggregate solely composed of the [PRM-A(2)/Ca(2+)/Man-OMe(2)] complex. The simple 1:1 complexes of biosynthetically (13)C-enriched PRM-As and [(13)C(6)]Man-OMe facilitated the analysis of the primary Man binding of PRM-A by two-dimensional dipolar-assisted rotational resonance (2D-DARR), which clearly identified that the cavity consisted of D-alanine moiety and ABC rings of PRM-A is the Man binding site. Interestingly, the proposed Man binding site of PRM-A seems to resemble the typical architecture of artificial carbohydrate receptors.     

Confinement in carbon nanospace-induced production of KI nanocrystals of high-pressure phase

An outstanding compression function for materials preparation exhibited by nanospaces of single-walled carbon nanohorns (SWCNHs) was studied using the B1-to-B2 solid phase transition of KI crystals at 1.9 GPa. High-resolution transmission electron microscopy and synchrotron X-ray diffraction examinations provided evidence that KI nanocrystals doped in the nanotube spaces of SWCNHs at pressures below 0.1 MPa had the super-high-pressure B2 phase structure, which is induced at pressures above 1.9 GPa in bulk KI crystals. This finding of the supercompression function of the carbon nanotubular spaces can lead to the development of a new compression-free route to precious materials whose syntheses require the application of high pressure.     

Investigation of thermal hazard during the hydrosilylation of 1,6-divinyl(perfluorohexane) with trichlorosilane

In this study, we examined the reaction hazard during the hydrosilylation reaction between trichlorosilane (TCS) and 1,6-divinyl(perfluorohexane) (FDV) in the presence of a butanol solution of chloroplatinic acid (Pt-Cat) as the catalyst. Assuming the three industrial risks of excessive addition of Pt-Cat, contamination by iron rust and mixing with cooling water, we observed the temperature and pressure change of TCS/FDV with an excessive amount of Pt-Cat, TCS/FDV/Pt-Cat with Fe₂O₃ and TCS/FDV/Pt-Cat with distilled water, using an accelerating rate calorimeter (ARC). The temperature and pressure greatly increased, especially in the sample with Fe₂O₃. For instance, in TCS/FDV/Pt-Cat with 1.5 wt.% Fe₂O₃, the heat release rate exceeded 624 K · min^?1 and the pressure rose above 25 MPa during the exothermic reaction.     

An LC method for quantifying bepridil in human plasma using 1-naphthol as the internal standard

A modified method for the quantitative determination of bepridil hydrochloride in human plasma is described. This method is unrelated to chemical methods currently in use. The mobile phase is 50 mM phosphate buffer (pH3.0)-methanol-acetonitrile-triethylamine (57:3:40:1, v/v), and the samples are fractionated on a C8-3 column (150 × 4.6 mm, 5 μm) using a flow rate of 0.9 mL/min. Bepridil was detected by UV spectroscopy at 254 nm. The retention times of bepridil and 1-naphthol were 12.6 min and 7.5 min, respectively; there was no interference originating from human plasma. We confirmed that the bepridil and 1-naphthol peaks were not influenced by the presence of 32 commercial medicines frequently co-administered with bepridil. Additionally, the concentration of bepridil in the plasma of five patients treated with bepridil for atrial fibrillation was measured. These samples were collected just before each dosage of bepridil. Their rhythm and rate control were well maintained. Trough concentrations ranged from 233.9 to 347.4 ng/mL, similar to previously reported values.     

(S)-stereoisomer of telomestatin as a potent G-quadruplex binder and telomerase inhibitor

Total synthesis of the (S)-stereoisomer of telomestatin (1) was accomplished. (S)-Telomestatin exhibited potency four times that of the natural product, (R)-telomestatin, which was the most potent telomerase inhibitor previously reported. In the circular dichroism spectral analysis of the complexes possessing randomly structured single-stranded d[TTAGGG](4) oligonucleotide, (S)-telomestatin, like (R)-telomestatin, induced an antiparallel G-quadruplex structure. The melting temperature (T(m)) value of the (S)-isomer complex was greater than that of the (R)-telomestatin complex. Therefore, it is concluded that the stereochemistry of the thiazoline of telomestatin is important to the binding ability of a G-quadruplex binder, and (S)-telomestatin as a G-quadruplex binder is more potent than the natural product.     

Efficient synthesis of [¹¹C]ramelteon as a positron emission tomography probe for imaging melatonin receptors involved in circadian rhythms

Ramelteon (TAK-375) is a novel melatonin receptor agonist that is used for clinical treatment of insomnia. The present report describes radiolabeling of ramelteon with the short-lived positron-emitter 11C (T(1/2)=20.4 min) by 2 methods. One method was [11C]methylation of an acetoamide precursor and the other was [11C]acylation of the corresponding amine precursor. First, [11C]methylation method showed the low reproducibility together with the production of many kinds of side products from which the [11C-methyl]Ramelteon was separated with chemical purity of <28% and radiochemical purity of >98%. Whereas, the [11C]acylation method showed high efficiency and reproducibility with a good radiochemical yield (22-43%, decay corrected), high chemical and radiochemical purities (>99% each), and high specific activity (43-162 GBq/μmol) (n=5) after HPLC purification. [11C]Ramelteon is a potential positron emission tomography (PET) probe for imaging the melatonin receptor.