Polycyclic N‐Heterocyclic Compounds. Part 81: Synthesis and Evaluation of Pentacyclic 1,2,4,5‐Tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]imidazo[1,2‐c]pyrimidine and Related Compounds as Potential Antiplatelet Aggregators

Dehydrative ring closure reactions were carried out on fused 4‐(2‐hydroxyethylamino) (or 2‐hydroxyethoxy or 2‐hydroxyethylthio)pyrimidines ( 2a , 2b , 2c ) to give fused 2,3‐dihydroimidazo[1,2‐c] (or 2,3‐dihydrooxazolo[3,2‐c] or 2,3‐dihydrothiazolo[3,2‐c])pyrimidines. This reaction produced the pentacyclic 1,2,4,5‐tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]imidazo[1,2‐c]pyrimidine ( 3a ) and 1,2,4,5‐tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]thiazolo[3,2‐c]pyrimidinium chloride ( 3c ) from the 2‐hydroxyethylamino‐derivative and 2‐hydroxyethylthio‐derivative, respectively. In contrast, 2‐hydroxyethoxy‐derivative ( 2b ) gave the rearrangement product, 3‐(2‐chloroethyl)‐5,6‐dihydro[1]benzothieno[3′,2′:2,3]thiepino[4,5‐d]pyrimidin‐4(3H)‐one ( 4 ). Effects of the synthesized compounds on collagen‐induced platelet aggregation were also evaluated.     

Polycyclic N‐Heterocyclic Compounds. Part 80: Synthesis and Evaluation of Effects on In Vitro Pentosidine Formation of 5,6‐Dihydro[1]benzothieno[3′,2′:2,3]thiepino[4,5‐d]pyrimidine and Related Compounds

Reaction of 3‐(3‐cyanopropylthio)[1]benzothiophene‐2‐carbonitrile with tert‐BuONa gave 5‐amino‐1,2‐dihydro[1]benzothieno[3,2‐d]thieno[2,3‐b]pyridine and 5‐amino‐2,3‐dihydro[1]benzothieno[3,2‐b]thiepin‐4‐carbonitrile. The latter compound served as a convenient scaffold for the synthesis of the new heterocycles, [1]benzothieno[3′,2′:2,3]thiepino[4,5‐d]pyrimidines. All of our new tetracyclic products were evaluated for in vitro inhibitory activity on the formation of pentosidine, which is one of representative advanced glycation end products.     

Control of the Transition between Ni‐C and Ni‐SIa States by the Redox State of the Proximal Fe?S Cluster in the Catalytic Cycle of [NiFe] Hydrogenase

[NiFe] hydrogenase catalyzes the reversible cleavage of H₂. The electrons produced by the H₂ cleavage pass through three Fe–S clusters in [NiFe] hydrogenase to its redox partner. It has been reported that the Ni‐SI_a, Ni‐C, and Ni‐R states of [NiFe] hydrogenase are involved in the catalytic cycle, although the mechanism and regulation of the transition between the Ni‐C and Ni‐SI_a states remain unrevealed. In this study, the FT‐IR spectra under light irradiation at 138–198 K show that the Ni‐L state of [NiFe] hydrogenase is an intermediate between the transition of the Ni‐C and Ni‐SI_a states. The transition of the Ni‐C state to the Ni‐SI_a state occurred when the proximal [Fe₄S₄]_p^2+/+ cluster was oxidized, but not when it was reduced. These results show that the catalytic cycle of [NiFe] hydrogenase is controlled by the redox state of its [Fe₄S₄]_p^2+/+ cluster, which may function as a gate for the electron flow from the NiFe active site to the redox partner.     

A Bioanode Using Thermostable Alcohol Dehydrogenase for an Ethanol Biofuel Cell Operating at High Temperatures

To extend the range of biofuel cell applications, we wish to increase their maximum operational temperatures. Using a thermostable alcohol dehydrogenase as a biocatalyst, we prepared an enzyme‐immobilized bioanode that can operate at high temperatures. The catalytic current for ethanol oxidation was increased using this electrode at temperatures up to 80 °C.     

Iterative molecular assembly based on the cation-pool method. Convergent synthesis of dendritic molecules

An iterative method for molecular assembly has been developed based on the cation-pool method using (trimethylsilyl)diphenylmethane as a building block. The silyl group works as both an activating group of the benzene ring in the Friedel-Crafts type reaction and an electroauxiliary in the subsequent low temperature anodic oxidation to generate dendritic diarylcarbenium ions, which were well characterized by low-temperature NMR spectroscopy. The convergent synthesis of dendritic molecules has been achieved by repeating the sequence.     

(1)H-NMR study of ternary platinum(II) complexes with N-(1-Naphtyl)methyl-1,2-ethanediamine or N-(9-anthrylmethyl)-1,2-ethanediamine and bipyridine or phenanthroline and restricted single bond rotation due to aromatic-aromatic ring interaction

(1)H-NMR spectra of square-planar complexes with the formula [Pt(L(1))(L(2))]X(2) where L(1) is 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen) and L(2) is N-(1-naphthyl)methyl-1,2-ethanediamine (Npen) or N-(9-anthryl)methyl-1,2-ethanediamine (Aten) indicate that the N-naphthylmethyl and N-anthrylmethyl groups are forced to adopt a pseudo axial disposition due to intramolecular repulsion of hydrogen atoms of the aromatic diimines. The aromatic-aromatic interactions in the N-arylmethyl-1,2-ethanediamine complexes and aromatic diimines caused them to undergo intramolecular stacking. (1)H-NMR spectra of these complexes showed a significant concentration and temperature dependence. The monomer-dimer equilibrium was estimated, based on the concentration dependency. Restricted single bond rotation was estimated from temperature dependency data. The rotation of the anthracene ring of the [Pt(bpy)(Aten)](2+) complex showed an activation energy of ca. 38 kJ mol(-1), which is in good agreement with a mechanism involving successive rotations about single bonds with restriction by intramolecular aromatic-aromatic ring interactions.     

Sesquiterpenoids isolated from Eupatorium glehnii. Isolation of guaiaglehnin A, structure revision of Hiyodorilactone B, and genetic comparison

A new sesquiterpenoid substituted with unsaturated ester, guaiaglehnin A (1), along with 15 previously known compounds, were isolated from the methanol extract of the terrestrial part of Eupatorium glehnii (Compositae) collected in Nagano Prefecture, Japan, the results of which supported the previous study by Takahashi et al. The chemical constituents of E. glehnii collected in Nagano Prefecture and those collected in Tokushima or Hokkaido are quite different, depending on collection site, although the species are identical. The base sequences of three different samples were identical. Diversity in the chemical components was detected, though no diversity existed in the DNA sequence. In this study, eupasimplicin A (2) was also isolated, whose presence in the extract of E. chinense simplicifolium was recorded but not in an article. The side chain geometry of hiyodorilactone B (5) was revised to be E.     

New Secoiridoid Glucosides from Swertia japonica

Four new secoiridoid glucosides, swertiajaposides C–F ( 1 – 4 , resp.), were isolated from the whole plant of Swertia japonica Makino together with two known compounds, 8‐hydroxy‐10‐hydrosweroside ( 5 ) and senburiside IV ( 6 ). The structures of 1 – 4 were elucidated on the basis of spectroscopic, chemical, and physicochemical evidence.     

Albumin-mediated selenium transfer by a selenotrisulfide relay mechanism

In this study, we demonstrated a human serum albumin (HSA)-mediated selenium transfer; the selenium exported from red blood cells (RBCs) was bound to HSA through the selenotrisulfide and then transferred into the hepatocyte. After the treatment of the RBCs with selenite, the selenium efflux from the RBCs occurred in an HSA concentration-dependent manner. Pretreatment of HSA with iodoacetamide almost completely inhibited the selenium efflux from the RBC to the HSA solution. The selenium efflux experiment was carried out in an HSA solution (45 mg/mL), and subsequently the HSA solution was subjected to gel permeation chromatographic separation. The peak fraction of the selenium content was consistent with that of the HSA. The selenium bound to HSA in this solution was completely eliminated by a treatment with penicillamine (Pen), which resulted in the generation of penicillamine selenotrisulfide, PenSSeSPen. The selenium efflux from the RBCs was also occurred in a Pen solution, and PenSSeSPen was observed in the resulting Pen solution. The selenium exported from the RBC was thought to bind to the HSA via a selenotrisulfide linkage with its single free thiol. A model of the selenium-bound HSA was prepared by the reaction of the HSA with PenSSeSPen. The selenium from PenSSeSPen can bind to HSA by a thiol exchange between Pen and the free thiol of HSA, which produces the selenotrisulfide-containing HSA (HSA-SSeSPen). When HSA-SSeSPen was incubated with isolated rat hepatocytes, the selenium content in the hepatocytes increased along with its decrease in the incubation medium. To verify the results from the model experiments using HSA-SSeSPen, we conducted the HSA-mediated selenium transfer experiment from RBC treated with selenite to the hepatocytes. The selenotrisulfide-containing HSA was able to transport the selenium into the hepatocyte. Overall, the selenium transfer from the RBC to the hepatocytes involves a relay mechanism of thiol exchange that occurs between the selenotrisulfide and thiol compounds (selenotrisulfide relay mechanism: R-SSeS-R + HSA-SH --> HSA-SSeS-R + R'-SH --> R-SSeS-R').