Synthesis and structure-activity relationships of N-substituted 2-[(2-imidazolylsulfinyl)methyl]anilines as a new class of gastric H+/K(+)-ATPase inhibitors.

A series of N-substituted 2-[(2-imidazolylsulfinyl)methyl]anilines (3) was synthesized and evaluated for its biological activity against gastric H+/K(+)-ATPase prepared from rabbit stomach and gastric acid secretions in Heidenhain pouch dogs. Monoalkyl substituents on the nitrogen atom of the aniline moiety markedly inhibited the enzyme activity to the same degree as omeprazole, a representative H+/K(+)-ATPase inhibitor. Most of these compounds, administered at 3 mg/kg i.v. inhibited histamine-stimulated gastric acid secretion. The inhibitory activity of these derivatives on the enzymes at pH 6.0 was more potent than that at pH 7.4, and was distinctly correlated to stability in aqueous solution at pH 5.0.     

Synthesis of two naturally occurring 3-methyl-2,5-dihydro-1-benzoxepin carboxylic acids

[structures: see text] Two naturally occurring 3-methyl-2,5-dihydro-1-benzoxepin carboxylic acids, 6-hydroxy-3-methyl-8-(phenylethyl)-2,5-dihydro-1-benzoxepin-9-carboxylic acid (radulanin E) (1) and 9-hydroxy-3-methyl-2,5-dihydro-1-benzoxepin-7-carboxylic acid (2), were synthesized using Stille coupling followed by Mitsunobu cyclization.     

Antioxidant activity and Neurite outgrowth-enhancing activity of scorbamic acid and a red pigment derived from ascorbic acid

Abstract

L-Ascorbic acid (AA), known as vitamin C, can form browning products by a non-enzymatic process during storage and the browning products cause deterioration of agricultural products. In the browning reaction, a red pigment, 2,2´-nitrilodi-2(2´)-deoxy-L-ascorbic acid ammonium salt (NDA), is generated from AA via L-scorbamic acid (SCA) as an intermediate. However, the biological activities of SCA and NDA have not yet been clarified. In this study, we assayed the antioxidant activities of SCA and NDA using ABTS radical cation and their neurite outgrowth-enhancing activities in PC12 cells. SCA showed stronger radical-scavenging activity than that of AA, while NDA hardly showed any activity. SCA and NDA enhanced the neurite outgrowth induced by dibutyryl cyclic AMP after their incorporation into cells in the same manner as that of AA. The results indicated that SCA has antioxidant activity and that SCA and NDA have neurite outgrowth-enhancing activity.     

Synthesis of 15alpha-fluoro-24,25-dihydrolanosterol as a potential inhibitor and/or mechanistic probe for lanosterol 14alpha-demethylase

As a potential inhibitor and/or mechanistic probe for lanosterol 14alpha-demethylase, 15alpha-fluoro-24,25-dihydrolanosterol was prepared by fluorination of 15alpha-hydroxy-24,25-dihydrolanost-7-en-3beta-yl benzoate with diethylaminosulfur trifluoride, followed by hydrogen chloride-catalyzed isomerization of the delta7 to delta8 and reductive cleavage of the benzoate.     

Zirconium-catalyzed chemoselective methylalumination of ethers, amines, and sulfides bearing two terminal alkenyl groups

Chemoselectivity in the methylalumination reaction of unsymmetrical ethers, amines, and sulfides bearing two different terminal alkenyl groups, a 13-tetradecenyl group and an allyl, 4-pentenyl or 6-heptenyl group was examined. The methylalumination of the allyl derivatives proceeded with complete chemoselectivity to afford only the 13-tetradecenyl-monomethylated products. In the methylalumination reactions of the 4-pentenyl and the 6-heptenyl derivatives, in addition to the 13-tetradecenyl-monomethylated products, and dimethylated products were also obtained. However, as in the case of the allyl derivatives, monomethylation to the shorter 4-pentenyl or 6-heptenyl group was not observed, except in the case of 6-heptenyl 13-tetradecenyl amine. The unique selectivity was rationalized upon how readily the intramolecular ligand exchange reaction between intermediate zirconocenium-alkene and zirconocenium-heteroatom complexes could occur.     

Precise control and consecutive modulation of spin transition temperature using chemical migration in porous coordination polymers

Precise control of spin transition temperature (T(c)) is one of the most important challenges in molecular magnetism. A Hofmann-type porous coordination polymer {Fe(pz)[Pt(II)(CN)(4)]} (1; pz = pyrazine) exhibited cooperative spin transition near room temperature (T(c)(up) = 304 K and T(c)(down) = 284 K) and its iodine adduct {Fe(pz)[Pt(II/IV)(CN)(4)(I)]} (1-I), prepared by oxidative addition of iodine to the open metal sites of Pt(II), raised the T(c) by 100 K. DSC and microscopic Raman spectra of a solid mixture of 1-I and 1 revealed that iodine migrated from 1-I to 1 through the grain boundary after heating above 398 K. We have succeeded in precisely controlling the iodine content of {Fe(pz)[Pt(CN)(4)(I)(n)]} (1-In; n = 0.0-1.0), which resulted in consecutive modulation of T(c) in the range 300-400 K while maintaining the hysteresis width. Furthermore, it was demonstrated that iodine migration in the solid mixture was triggered by the spin transition of 1-I. The magnetically bistable porous framework decorating guest interactive open-metal-site in the pore surface makes it possible to modulate T(c) ad arbitrium through unique postsynthetic method using iodine migration.     

Mechanoluminescent light source for a fluorescent probe molecule

We have demonstrated an innovative ability of mechanoluminescent (ML) material as a light source for the first time. By appropriate smart size control and nondestructive mechanical stimulation, the ML particle can be considered a promising candidate of in situ light source for bio-imaging and photo-therapy even in a human body.     

Chichibabin pyridinium synthesis

Chichibabin pyridine synthesis involves the reaction of three aldehydes and ammonia to form 2,3,5-trisubstituted pyridines. This study examined the synthesis of tetrasubstituted pyridinium from aldehydes and an amine hydrochloride in the presence/absence of Pr(OTf)₃. Important insights into the reaction mechanisms of Chichibabin pyridinium synthesis were proposed through the investigation of reaction intermediates along with quantitative GC–MS analysis.     

Visible-Light-Induced Heptacene Generation under Ambient Conditions: Utilization of Single-crystal Interior as an Isolated Reaction Site

The photo-induced generation of unstable molecules generally requires stringent conditions to prevent oxidation and the concomitant decomposition of the products. The visible-light-induced conversion of two heptacene precursors to heptacene was studied. Single crystals of bis- and mono-α-diketone-type heptacene precursors ( 7-DK2 and 7-DK1 , respectively), were prepared to investigate the effect of precursor structure on reactivity. The photoirradiation of a 7-DK2 single crystal cleaved only one α-diketone group, forming an intermediate bearing a pentacene subunit, while that of a 7-DK1 single crystal gave rise to characteristic absorption peaks of heptacene and their increase in intensity with photoirradiation time, indicating the generation of heptacene without decomposition. Heptacene production was not observed when the precursors were photoirradiated in solution, implying that the single crystal interior provided isolation from the external environment, thus preventing heptacene oxidation.     

Estimation of single-nucleotide polymorphism allele frequency by alternately binding probe competitive polymerase chain reaction

A modified solvent microextraction with back extraction method (SME/BE) combined with high performance liquid chromatography and fluorescence detection (HPLC-FD) was developed for the determination of citalopram in human plasma. Extraction process was performed in a home-made total glass vial without using a teflon ring, usually employed in SME/BE. Citalopram was first extracted from 0.5 mL of plasma, modified with sodium hydroxide, into hexane. Back extraction step was then performed into 5.2 μL of 45 mM ammonium formate solution (pH 4) using a GC microsyringe. The extract was subsequently transferred into a liner-like vial and then injected into the HPLC system. An enrichment factor of 150 along with a good sample clean-up was obtained. The calibration curve showed linearity in the range of 1.0–130.0 ng mL⁻¹ with regression coefficient corresponding to 0.992. This range covers therapeutic window and even lower amounts which is important in pharmacokinetic studies. Limits of detection and quantification, based on a signal to noise ratio (S/N) of 3 and 10, were 0.3 and 0.8 ng mL⁻¹, respectively. The method was also applied for the determination of citalopram in plasma samples after oral administration of 40 mg single dose of citalopram.