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A highly stereoselective asymmetric total synthesis of (-)-jimenezin (

Many rainwater harvesting systems have been installed and operated to supply drinking water to rural regions. However, they often lacked the management method to supply safe and reliable drinking water. The current practice of operating rainwater harvesting systems did not have systematic monitoring as the basis of reliable operation so that the operators did not have confidence in their operation. To overcome these limitations, a rainwater for drinking (RFD) system has been suggested which was to produce drinking water by adding the proper treatment processes and setting up the proper operational mode. This study aimed to evaluate stable regular monitoring results from a pilot RFD system at a local hospital in Vietnam. Water quality and quantity were monitored by the trained local operator on a quarterly and weekly basis. The raw dataset was then shared with the study team by uploading into an open data access platform, from where the technical support was provided to prevent the provision of unsafe water to users. Ultimately, employing systematic monitoring would help to enhance the resilience of the RFD system, contributing to resolving the drinking water issue in rural areas of developing countries, aiming at the achievement of Sustainable Development Goal 6. HIGHLIGHTS Rainwater can be a viable drinking water supply option in developing countries.; A pilot rainwater for drinking (RFD) system has been in operation successfully at a rural hospital in Vietnam.; A weekly and quarterly monitoring system by the local operators was developed for safe and reliable operation.; Open data sharing was also developed and used for distance technical support.; This systematic monitoring system can enhance the resilience of future RFD systems.

A branch connecting two neighboring ferromagnetic α 1-phase rods is one of the geometric factors that contributes to degradation of alnico's normally high coercivity. This letter investigates the effects of various branch geometries and dimensions on the coercivity of alnico comprehensively by using a micromagnetic simulator when the branch is assumed to be connected in either H- or U-shaped alnico structure and the magnetization reversal of the ferromagnetic α 1-phase rod occurs by quasi-coherent rotation or curling. For the H-shaped structure, high coercivity is realized by adopting the middle-branch-connected (MBC) structure with a long branch length and width for quasi-coherent rotation, regardless of the branch thickness. For curling, the same geometric parameters are suggested except for a thick branch thickness. For the U-shaped structure with quasi-coherent rotation, a short branch thickness, width, and length, and MBC position lead a high coercivity. For curling, a short branch width but long length and edge-bridge-connected position result in a high coercivity, regardless of the branch thickness.

This study aims to develop new potential therapeutic moracin M prodrugs acting on lung inflammatory disorders. Potential moracin M prodrugs (KW01-KW07) were chemically synthesized to obtain potent orally active derivatives, and their pharmacological activities against lung inflammation were, for the first time, examined in vivo using lipopolysaccharide (LPS)-induced acute lung injury model. In addition, the metabolism of KW02 was also investigated using microsomal stability test and pharmacokinetic study in rats. When orally administered, some of these compounds (30 mg/kg) showed higher inhibitory action against LPSinduced lung inflammation in mice compared to moracin M. Of them, 2-(3,5-bis((dimethylcarbamoyl)oxy)phenyl)benzofuran-6-yl acetate (KW02) showed potent and dose-dependent inhibitory effect on the same animal model of lung inflammation at 1, 3, and 10 mg/kg. This compound at 10 mg/kg also significantly reduced IL-1β concentration in the bronchoalveolar lavage fluid of the inflamed-lungs. KW02 was rapidly metabolized to 5-(6-hydroxybenzofuran-2-yl)-1,3-phenylene bis(dimethylcarbamate) (KW06) and moracin M when it was incubated with rat serum and liver microsome as expected. When KW02 was administered to rats via intravenous or oral route, KW06 was detected in the serum as a metabolite. Thus, it is concluded that KW02 has potent inhibitory action against LPS-induced lung inflammation. It could behave as a potential prodrug of moracin M to effectively treat lung inflammatory disorders.

Anaplastic lymphoma kinase (ALK), which belongs to the insulin receptor tyrosine kinase superfamily, plays an important role in nervous system development. Due to chromosomal translocations, point mutations, and gene amplification, constitutively activated ALK has been implicated in a variety of human cancers, including anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer, and neuroblastoma. We evaluated the anti-cancer activity of the ALK inhibitor KRCA-0008 using ALCL cell lines that express NPM (nucleophosmin)-ALK. KRCA-0008 strongly suppressed the proliferation and survival of NPM-ALK-positive ALCL cells. Additionally, it induced G0/G1 cell cycle arrest and apoptosis by blocking downstream signals including STAT3, Akt, and ERK1/2. Tumor growth was strongly suppressed in mice inoculated with Karpas-299 tumor xenografts and orally treated with KRCA-0008 (50 mg/kg, BID) for 2 weeks. Our results suggest that KRCA-0008 will be useful in further investigations of ALK signaling, and may provide therapeutic opportunities for NPM-ALK-positive ALCL patients.

Natural-derived steroids and their analogues are present in various plants and insects. To minimize the chance of missing a positive doping test and avoiding potentially serious health problems, adequate screening methods are necessary for the detection of a wide range of natural-derived steroids and their analogues in dietary supplements. In this study, an accurate and simple liquid-chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine and quantify the natural-derived steroids and their analogues according to the International Conference on Harmonization of technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The validation results indicating excellent extraction efficiency and low matrix effects show that the LC-MS/MS method is reliable for the detection of natural-derived steroids and their analogues. In addition, we established the ion fragmentation of turkesterone and ion fragmentation of four natural-derived steroids and their analogues. The validated method was applied to 60 dietary supplements purchased online and in person from international vendors in 2020. Ecdysterone and 5α-hydroxylaxogenin were detected respectively in 3 and 14 of 60 dietary supplements. Especially, a high amount of 5α-hydroxylaxogenin, an FDA-unapproved ingredient, was detected in two of dietary supplements (44.4 and 32.3 mg/g). This component should be controlled since it may cause unexpected side effects if administered excessively. Thus, this method will be helpful for the continuous control and supervision of unlicensed dietary supplements containing natural-derived steroids and their analogues.

Tropomyosin receptor kinase A (TrkA) protein is a receptor tyrosine kinase encoded by the

Quaternary AlCoCrNi alloy was designed by removing the heavy constituent of Fe from the dual-phase AlCoCrFeNi high-entropy alloy to achieve low density with good mechanical properties. The AlCoCrNi alloy exhibited a nano-scale dual-phase structure consisted of Cr-rich A2 and Ni(Co)-Al-rich B2 phases with a high degree of coherence in both dendritic and interdendritic regions. In particular, the Ni(Co)-Al-rich B2 phase revealed the non-stoichiometric composition between the Ni and the Al, which deviated with the Ni-Al-rich B2 phase with a stoichiometric composition in the previous AlCoCrFeNi high-entropy alloy. The chemical evolution in the constituent phases strongly affected the mechanical properties of the dual-phase high-entropy alloy. Based on these microstructural features of the AlCoCrNi alloy, the mechanical properties were systematically investigated at wide temperature ranges.

The present study aimed to purify and identify the metabolites from T. atroviride using high-performance liquid chromatography (HPLC) and 1H and 13C nuclear magnetic resonance spectrometer (NMR) followed by analyzing their toxicological, antibacterial and anticancer properties. This work identified two metabolites - TM1 and TM2. TM1 was in two forms: (i) 1, 3-dione-5, 5-dimethylcyclohexane; and, (ii) 2-enone-3hydroxy -5,5-dimethylcylohex, while TM2 was 4H-1,3-dioxin-4-one-2,3,6-trimethyl. These metabolites did not exhibit any irritant or allergic reaction as revealed by HET- CAM test. TM2 significantly inhibited the growth of H. pylori and Shigella toxin producing Escherichia coli (STEC) as evident by in vitro and microscopic observations of bacterial cell death. TM2 also induced the cell death and cytotoxicity, as revealed by cell viability test and western blot analysis. According to microscopic, flow cytometer and western blot analysis, TM2 treated cells displayed higher ROS, cell death, and apoptosis-related protein expression than TM1 and control. This study concluded that TM2 derived from T. atroviride was a potential therapeutic agent for anti-prostate cancer and antibiotic agent against MDR- H. pylori and STEC and it is also recommended to carry out further in vivo animal model experiments with improved stability of the metabolites for future pharmaceutical trails.

Selective androgen receptor modulators (SARMs) are compounds with specific androgenic properties that have been investigated for the treatment of conditions such as muscle wasting disease. The reported androgenic properties have resulted in their use by athletes, and consequently they have been on the World Anti-Doping Agency prohibited list for more than a decade. To minimise the chance of an unattended positive doping test and to avoid potential serious health problems, adequate screening methods for the detection of a wide range of SARMs in these supplements is necessary. In this study, a rapid and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated simultaneously to screen and quantify six SARMs in dietary supplements, with confirmation by liquid chromatography-quadrupole-time of flight mass spectrometry (LC-Q-TOF/MS). The validated method was applied to 60 dietary supplements obtained by on-line and direct purchase from international vendors in 2020. Various SARMs were detected at high concentrations in 20 products which were advertised as having androgenic properties. For example, andarine was present at 7.2% in one product, and GW501516 was found at 3.49% in the another product. Furthermore, MK-677 and YK-11, not disclosed on the label, were detected in some products. YK-11 is easily hydrolysed in just a few hours. Although YK-11 is particularly unstable, such that the protonated ion [M + H]

Sphingosine 1-phosphate (S1P) receptors (S1PRs) are a group of G protein-coupled receptors that confer a broad range of functional effects in chronic inflammatory diseases and metabolic diseases. S1PRs may also be involved in the development of non-alcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear. Here we show that the livers of various mouse models of NASH as well as Kupffer cells had a particularly strong expression of S1pr4. Accordingly, genetic depletion of S1pr4 protected the mice against hepatic inflammation and fibrosis. Moreover, SLB736, a novel selective functional antagonist of SIPR4 prevented diet-induced NASH in mice without lymphopenia. S1P increased the expression of S1pr4 in Kupffer cells and activated the NLRP3 inflammasome through PLC/IP3/IP3R-dependent [Ca++] signaling. SLB736 treatment or S1pr4 depletion in Kupffer cells inhibited LPS-mediated Ca++ release and deactivated the NLRP3 inflammasome. S1PR4 antagonism may be a novel therapeutic strategy for NASH.

Fibrillar aggregates of amyloid-β (Aβ) are the main component of plaques lining the cerebrovasculature in cerebral amyloid angiopathy. As the predominant Aβ isoform in vascular deposits, Aβ40 is a valuable target in cerebral amyloid angiopathy research. However, the slow process of Aβ40 aggregation in vitro is a bottleneck in the search for Aβ-targeting molecules. In this study, we sought a method to accelerate the aggregation of Aβ40 in vitro, to improve experimental screening procedures. We evaluated the aggregating ability of bicine, a biological buffer, using various in vitro methods. Our data suggest that bicine promotes the aggregation of Aβ40 with high speed and reproducibility, yielding a mixture of aggregates with significant β-sheet-rich fibril formation and toxicity.

The cross-metathesis (CM) of methallyl halides catalyzed using four different ruthenium-based complexes-Grubbs catalyst, Grubbs second-generation catalyst, Hoveyda-Grubbs second-generation catalyst, and Stewart-Grubbs catalyst-was investigated. When methallyl chloride or bromide was reacted with a model substrate containing a benzyl ether group, the Grubbs catalyst, and Grubbs second-generation catalyst did not promote the reaction well. However, the Hoveyda-Grubbs second-generation catalyst and Stewart-Grubbs catalyst afforded the corresponding products in moderate to good yield with moderate E/Z selectivity. Accordingly, several functionalized methallyl halides were prepared by CM. Various functional groups were well-tolerated in this system when the Stewart-Grubbs catalyst was used. To demonstrate the practical utility of our method, methallyl halide CM was successfully employed for the formal total synthesis of a natural product (-)-presphaerene, in which the precursor of the key cyclopentanecarboxylate intermediate was efficiently prepared in three steps.

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.

A new sildenafil analogue was detected during routine screening of dietary supplements suspected to be adulterated with an erectile dysfunction drug(s) using HPLC-DAD. The UV spectrum of this compound was highly similar to that of sildenafil and almost identical to that of desmethylpiperazinyl sildenafil. The analogue was purified by using semi-preparative HPLC and structurally elucidated by performing mass spectrometric and NMR spectroscopic experiments. The spectral data revealed that this sildenafil analogue bears an n-propoxy group instead of an ethoxy group and possesses no methylpiperazinyl moiety. The isolated compound, structure of which was further confirmed by spectral comparison with synthetic one, was thus named as desmethylpiperazinyl propoxysildenafil.

A series of Cu–M color alloys were investigated with two additional elements, Zn and Ga, that have adequate solubility to copper, which means that a wide region of solid-solution phase exists in the Cu-rich area in terms of color variation. To measure the color change of the alloys, the reflectivity difference analysis, the color difference and the transition energy were utilized. As the amount of minor alloying elements increased, the proportional relationship was found between the transition energy and the color difference compared to copper, for example, the color difference mounted with the increase of transition energy. A significant color difference was found when gallium was employed as the minor element. In other words, the influence of gallium on the color change was more evident than with Zn. It appears to be about 4.5 of the color difference when 3 at% of gallium was added.

A stereoselective protection-free asymmetric total synthesis of (+)-chamuvarinin (1), a potent anticancer and antitrypanosomal agent, has been accomplished. The adjacently linked [bis(tetrahydrofuran)]tetrahydropyran (THF-THF-THP) core of this natural product with seven stereogenic centers was constructed in a completely substrate-controlled fashion. The inter-ring stereochemistry ( threo,threo,threo) of the oxatricyclic core was established in a stereoselective fashion by a chelation-controlled Keck allylation, whereas the intraring cis or trans relative stereochemistry was controlled by a stereoselective internal alkylation.

This study aims to develop new potential therapeutic moracin M prodrugs acting on lung inflammatory disorders. Potential moracin M prodrugs (KW01-KW07) were chemically synthesized to obtain potent orally active derivatives, and their pharmacological activities against lung inflammation were, for the first time, examined in vivo using lipopolysaccharide (LPS)-induced acute lung injury model. In addition, the metabolism of KW02 was also investigated using microsomal stability test and pharmacokinetic study in rats. When orally administered, some of these compounds (30 mg/kg) showed higher inhibitory action against LPS-induced lung inflammation in mice compared to moracin M. Of them, 2-(3,5-bis((dimethylcarbamoyl)oxy)phenyl)benzofuran-6-yl acetate (KW02) showed potent and dose-dependent inhibitory effect on the same animal model of lung inflammation at 1, 3, and 10 mg/kg. This compound at 10 mg/kg also significantly reduced IL-1β concentration in the bronchoalveolar lavage fluid of the inflamed-lungs. KW02 was rapidly metabolized to 5-(6-hydroxybenzofuran-2-yl)-1,3-phenylene bis(dimethylcarbamate) (KW06) and moracin M when it was incubated with rat serum and liver microsome as expected. When KW02 was administered to rats via intravenous or oral route, KW06 was detected in the serum as a metabolite. Thus, it is concluded that KW02 has potent inhibitory action against LPS-induced lung inflammation. It could behave as a potential prodrug of moracin M to effectively treat lung inflammatory disorders.

Adiponectin is a major adipocytokine secreted from mammalian adipocytes. Relatively low expression of adiponectin is associated with various human metabolic diseases and some cancers. Adiponectin-secreting compounds have therapeutic potential for these diseases. Adipogenesis of human bone marrow-mesenchymal stem cells (hBM-MSCs) has been used as a phenotypic assay to find adiponectin secreting compounds. In a phytochemical library screen, 2-formyl-komarovicine, 1-(quinolin-8-yl)-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carbaldehyde, isolated from Nitraria komarovii was identified as a potential adiponectin-secreting compound. To validate the results of the impure phytochemical, we synthesized 2-formyl-komarovicine. The synthetic 2-formyl-komarovicine significantly promoted adiponectin production during adipogenesis in hBM-MSCs. In a target identification experiment, 2-formyl-komarovicine bound to peroxisome proliferator-activated receptor γ (PPARγ) in a concentration-dependent manner. Notably, 2-formyl-komarovicine competitively inhibited the adiponectin-promoting activity of a full PPARγ agonist, troglitazone, in hBM-MSCs, which is a pharmacological feature of a partial agonist. The ligand-docking model showed that 2-formyl-komarovicine interacted with the hydrophobic pocket of the PPARγ ligand-binding domain, but lacked an interaction to stabilize helix H12, which is one of the major binding themes of PPARγ partial agonists. We concluded that 2-formyl-komarovicine provides a novel pharmacophore for PPARγ partial agonists to increase adiponectin production.

Adamantan-1-yl 1-pentyl-1H-indazole-3-carboxylate (APINAC), a new synthetic cannabinoid, was recently isolated from a dietary supplement and identified in our laboratories. The metabolism and pharmacokinetics of APINAC were studied in vitro and in vivo with a rat model. APINAC (2.0 μM) was incubated with rat liver microsomes (RLMs) for up to 90 min to determine its phase I metabolic profile. APINAC was also administered to rats at a dose of 5 mg/kg intravenously (i.v.) or 10 mg/kg per os (p.o.). Blood samples were collected at specific time points, and urine samples were also collected for 1 day following APINAC administration. The analyses were conducted by both high- and low-resolution liquid chromatography–tandem mass spectrometry. Although APINAC was rapidly metabolized by RLMs (t 1/2, 15.2 ± 0.4 min), in vivo pharmacokinetic experiments in rats revealed moderate to long half-lives [11.3 h (i.v.) and 3.8 h (p.o.)]. A total of 22 APINAC metabolites could be detected in the RLMs and rat urine. APINAC was predominantly metabolized via ester hydrolysis to carboxylic acids M1 (with hydroxylation) and M18 (without hydroxylation), representative markers for APINAC intake. Hydroxylation of APINAC, with or without subsequent oxidation and glucuronidation, was observed in the case of the other metabolites. The diagnosis of illegal APINAC intake can be realized through the detection of several characteristic APINAC metabolites in human urine and/or APINAC itself in blood.

Over the past decades, mass spectrometry technologies have been developed to obtain mass accuracies of one ppm or less. Of the newly developed technologies, quadrupole time-of–flight mass spectrometry (Q-TOF–MS) has emerged as being well suited to routine and high-throughput analyses of pharmaceuticals. Dietary supplements and functional foods have frequently been found to be contaminated with pharmaceuticals. In our continuous efforts to develop methodologies to protect public health against adulterated dietary supplements, we have constructed a mass spectral database for 21 H1-antihistamines encountered as adulterants by using liquid chromatography-electrospray ionization (LC-ESI)/Q-TOF–MS, and have proposed their possible collision-induced dissociation pathways. This database will be very useful for the rapid and accurate detection of H1-antihistamines (known) and their analogues (unknown) illegally added to dietary supplements as well as in other sample matrices.

A number of phosphodiesterase 5 (PDE5) inhibitors approved by authorities have been used successfully in the treatment of erectile dysfunction. These medicines must be prescribed carefully due to their adverse effects, but they and their analogues are being illegally added to dietary supplements. These illegal dietary supplements pose a significant risk to public health. Several dimeric tadalafil analogues have been synthesized for use as reference standards in the inspection of functional foods that are mainly advertised as sexual enhancement products. During the course of this synthesis, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) was proven to be the reagent of choice for amide coupling to produce these dimeric tadalafil analogues. Moreover, the trans-isomer structures tentatively assigned for the isolated dimeric tadalafil analogues (bisprehomotadalafil and bisprecyclopentyltadalafil) found in dietary supplements are now revised to cis-isomer structures.

A new tadalafil analogue was found in a commercial dietary supplement for enhancing sexual performance. The compound was detected by a high-performance liquid chromatography-diode array detector (HPLC-DAD). The analogue was isolated using semi-preparative HPLC, and its accurate mass was established by two LC-high-resolution-mass spectrometers (LC-HRMS). The structure was determined by nuclear magnetic resonance (NMR) spectroscopy. The accurate mass of the compound corresponded to a molecular formula of C24H23N3O4. The compound was identified as a structural analogue of tadalafil in which the N-methyl group of tadalafil was replaced with an N-isopropyl group. We have named the new analogue isopropylnortadalafil and it is first reported herein.

Rare-earth free, ferromagnetic MnBi shows a positive temperature coefficient of coercivity from room temperature to 400 K and energy product (BH)max of 17.7 MGOe at 300 K. However, MnBi undergoes a first-order structural phase transformation from a ferromagnetic low-temperature phase (LTP) to a paramagnetic high-temperature phase at 613 K below the Curie temperature (Tc) of 716 K. The transformation is attributed to Mn diffusion into the interstitial site of LTP MnBi unit cell. Interstitial Mn antiferromagnetically couples with the Mn at lattice 2a site, lowering the magnetization. Cu-occupied bipyramidal sites are investigated as a possible means to suppress Mn diffusion into the bipyramidal sites using first-principles calculations based on the density functional theory. Saturation magnetization, magnetocrystalline anisotropy constant (K), and Tc of (Mn0.5Bi0.5)100−xCux (x = 0–33) are reported. The magnetocrystalline anisotropy changes to the out-of-plane direction (x = 13) from the in-plane direction (x = 0.0). Tc decreases gradually to 578 K at x = 33 from 716 K at x = 0.0. The calculations show a slightly lower (BH)max of 15.6 MGOe while it is expected that Cu-occupied interstitial sites will significantly suppress Mn diffusion and raise the temperature of the phase transformation.

Novel 1,2,3-triazole analogues (S7 ~ S10) were synthesized and evaluated for their inhibitory activity against hDPP-4. All the 1,2,3-triazole analogues exhibited moderate in vitro hDPP-4 inhibitory activities (265 ~ 780 nM). These results are somewhat less potent compared to those of known 1,2,3-triazole analogues (S1 ~ S6, 14 ~ 254 nM). S2 and S3 manifested excellent potency against hDPP-4 with IC50s of 28 and 14 nM, respectively. The role of the 1,2,3-triazole moiety in binding the molecule to the target was investigated using combined 10 1,2,3-triazole analogues (S1 ~ S10). Molecular dynamics (MD) simulations following the aforementioned docking phase were performed to elucidate potential binding modes of sitagliptin’s 1,2,3-triazole analogues in hDPP-4, with the use of a cocrystal structure of hDPP-4 with sitagliptin (PDB ID: 1X70). Docking and MD simulations of the complexes of hDPP-4 with sitagliptin, S2 and S3 suggest that Glu205, Glu206, Tyr662, and Tyr666 would be the key amino acid residues for the binding of the molecules with the receptor. Especially, S2 and S3 showed additional strong π-π interaction between Phe357 and 1,2,3-triazole. Same strong π-π interaction is also observed between Phe357 and the 1,2,4-triazole ring of sitagliptin. Furthermore, additional interactions with Tyr547, Cys551, and especially Arg358 would enhance the binding affinity of the compounds for the pocket of the enzyme. In overall, in vitro hDPP-4 inhibitory activities of synthetic 1,2,3-triazole analogues were well matched with results of computational simulations studies.

Two synthetic cannabinoid analogues were detected using high-performance liquid chromatography (HPLC)–diode array detector, and gas chromatography–time-of-flight-mass spectrometry during the inspection of illegal products in an airmail package. The analogues were separated by semi-preparative HPLC, and their structures were determined by performing liquid chromatography–high-resolution-mass spectrometry, infrared analysis, and nuclear magnetic resonance spectroscopy. Compound 1 was MDMB(N)-Bz-F, which has been reported previously. Compound 2 was elucidated as adamantan-1-yl 1-pentyl-1H-indazole-3-carboxylate (APINAC), in which the amide group of APINACA was replaced with an ester group. Because there has been no chemical or pharmacological data about this compound until now, this is the first report of its detection in illegal products.

A new tadalafil analogue was found, along with nortadalafil, using HPLC-DAD during the inspection of a health product sold without official approval. The analogue was separated using a semi-preparative HPLC system and its structure was determined by a combination of mass spectrometry and NMR spectroscopy. The compound was identified as a tadalafil analogue in which the N-methyl group of tadalafil was replaced with a tadalafil precursor moiety. Nuclear Overhauser effect spectroscopy experiments suggested a cis-relationship between the substituents on a piperidine ring in the tadalafil moiety.

The first total synthesis and structure revision of (-)-11β-hydroxycurvularin (1b), a macrolide possessing a β-hydroxyketone moiety, were accomplished. The β-hydroxyketone moiety in this natural product was introduced by cleavage of the N-O bond in an isoxazoline ring that was formed diastereoselectively in a 1,5-remote stereocontrolled fashion by employing intramolecular nitrile oxide cycloaddition.

Wollastonite-based bioceramic powders were synthesized by solid-state reaction between calcite and silica powder. To control the phase and bioactivity of wollastonite, we also prepared four kinds of wollastonite-based bioceramics by adding an enstatite (MgSiO3) powder. After solid state reaction at 1000-1300 degrees C, micron-sized powders were obtained by milling and screening. By using these powders, wollastonite coatings were fabricated on zirconia substrates by a room temperature spray process, and their microstructure and composition under different coating condition were investigated. Wollastonite coatings on zirconia substrates were formed with the homogeneous microstructure and nanoscaled grain size. The phase composition of the resultant wollastonite coatings was similar to that of the starting powders, however, the grain size of the wollastonite particles was reduced to about 100 nm due to their formation by particle impaction and fracture. The wollastonite coating layer exhibited bioactivity in a stimulated body fluid and forming ability of 25 nm sized-hydroxyapatite precipitates of during in vitro test in SBF solution.