A dual pathway in the solid-state photoreaction of nitrobenzaldehydes with indole

The solid-state photoreaction of the mixed crystals between nitrobenzaldehydes and indole was found to give nitrophenyl-(bis-3-indolyl)methane ( 3 ) and nitrophenyl-(3-indolyl)methanol ( 4 ). The structure of the ortho isomer 4c was established by X-ray crystallographic analysis. A dual pathway from an oxetane intermediate 5 is proposed for the formation of 3 and 4 .     

Study of temperature-responsibility on the surfaces of a thermo-responsive polymer modified stationary phase

We investigated a thermo-sensitive polymer, poly(N-isopropylacrylamide) (PNIPAAm), which is the basis of an HPLC stationary phase. We prepared a PNIPAAm terminally-modified surface. In this study, we investigated the effect of PNIPAAm on the surface of a stationary phase on separation based on changes of the retention time with the temperature step gradient. As the temperature changed the surface property of the stationary phase switched from hydrophilic to hydrophobic. The retention on the polymer-modified stationary phase remarkably changed upon changing the temperature. Using a column packed with PNIPAAm-modified silica, the separation of steroids was carried out by changing the temperature. With increasing temperature, an increased interaction between solutes and PNIPAAm-grafted surfaces of the stationary phases was observed. A temperature-dependent resolution of steroids was achieved using only water as a mobile phase. The PNIPAAm-modified surface of the stationary phase exhibited temperature-controlled hydrophilic-hydrophobic changes. The drastic and reversible surface hydrophilic-hydrophobic property alteration for PNIPAAm terminally-grafted surfaces should be due to rapid changes in the polymer hydration state around the polymer's transition temperature. A solvent gradient elution-like effect could be achieved with a single mobile phase by programmed temperature changes during chromatographic runs. This system should be highly useful to control the function and property of the stationary phase for HPLC only by changing the temperature with an aqueous solvent.     

Preparation and characterization of the inclusion complexes of equol with sulfobutylether-β-cyclodextrin: their antioxidant activity and dissolution evaluation

The formation of inclusion complexes between S-(?)-equol (SEq) and cyclodextrins (CDs) was investigated. The binding constant (K_c) of the SEq/sulfobutylether-β-cyclodextrin (SBE-β-CD) inclusion complex was determined to be 1600 L/mol based on UV data. The phenyl ring of the SEq molecule was found to be inserted from the secondary hydroxyl face of the SBE-β-CD as evidenced from ¹H–¹H rotating frame nuclear Overhauser effect spectroscopy (ROESY) NMR. The thermal properties of the solid SEq/SBE-β-CD inclusion complexes prepared by physical mixing, kneading and freeze-drying methods were studied by differential scanning calorimetry. For the solid complex obtained by the freeze-drying method, the endothermic peak corresponding to the melting point of SEq disappeared. The solid SEq/SBE-β-CD complexes exhibited a high score in antioxidant activity evaluation tests compared to SEq alone. Dissolution test revealed that the solid complex obtained by freeze-drying method had improved dissolution of SEq.     

SOLID-STATE PHOTOCHEMISTRY OF INDOLES WITH NAPTHALENE AND PHENANTHRENE

Abstract— Solid-state irradiation of mixed crystals prepared by meltinga 1:3 molar mixture of indole and phenanthrene followed by resolidifying the melt gave an adduct 2a in 13.5% yield. An adduct 2b was obtained by irradiation of the mixed crystals of 3-methylindole and phenanthrene. Irradiation of the same mixtures of indoles and phenanthrene in solution gave no photoproduct. Irradiation of the mixed crystals of indole and naphthalene gave a similar photoadduct 3a, which was also formed in solution. The 1:1 mixed crystals of indole and phenanthrene and of indole and naphthalene were characterized by various spectroscopic methods. Among them powder X-ray diffraction spectral analysis and differential scanning calorimetry revealed that the former mixed crystal is a simple mixture of microcrystals of indole and phenanthrene, while the latter forms a molecular compound.     

Determination of midazolam and its metabolite as a probe for cytochrome P450 3A4 phenotype by liquid chromatography-mass spectrometry

This study demonstrated the analysis of midazolam and its metabolites by liquid chromatography-mass spectrometry (LC-MS) with a sonic spray ionization (SSI) interface. The analytical column was a YMC-Pak Pro C18 (50 mm x 2.0 mm i.d.) using 10 mM ammonium acetate (pH 4.8)-methanol (1:1) at a flow rate of 0.2 ml min(-1). The drift voltage was 100 V. The sampling aperture was heated at 110 degrees C and the shield temperature was 230 degrees C. The lower limits for the detection of midazolam and 1'-hydroxymidazolam were 26.3 and 112.76 pg injected, respectively. The calibration curves for midazolam and 1'-hydroxymidazolam were linear in the range of 0.1-5 microg ml(-1). Within-day relative standard deviations was less than 7%. The method was applied to the determination of midazolam in monkey plasma, and the analysis of midazolam and its metabolites in an in vitro study with recombinant cytochrome P450 (CYP) 3A4. This method is sufficiently sensitive and useful to elucidate the kinetics of midazolam metabolite formation. We also investigated the effect of propofol on the metabolism of midazolam using recombinant CYP3A4. Propofol competitively inhibited the metabolism of midazolam to 1'-hydroxymidazolam by CYP3A4.     

Synthesis of the new mannosidase inhibitors, diversity-oriented 5-substituted swainsonine analogues, via stereoselective Mannich reaction

5alpha-substituted swainsonine analogues were synthesized by Mannich reaction of an in situ generated (-)-swainsonine iminium ion intermediate. 5alpha-substituted swainsonine analogues were epimerized to their 5beta-isomers in protic solvent. [reaction: see text]     

Synthesis of Immunosuppressive Neoglycoproteins: Bovine Serum Albumin Coupled with 8-(Hydrazino-Carbonyl)Octyl 4- Or 6-O-α-D-Mannopyranosyl-α-D-Mannopyranoside

Abstract

Recombinant cytokines generated by bacteria, especially E. coli, are nonglycosylated. To investigate the effects of carbohydrates on their activities, we attempted to develop new cytokines by introduction of carbohydrates. As a model we synthesized neoglycoproteins in which potential immunoregulatory carbohydrates were coupled to bovine serum albumin(BSA). Mannose dimers with C9 spacer, Manα1-6Man, which is reported to be immunosuppressive, and a reference substance Manα1-4Man were synthesized as follows. Benzylidenation of 8-(methoxycarbonyl)octyl α-D-mannopyranoside (10), followed by acetylation and cleavage of the benzylidene acetal, gave a glycosyl acceptor (13) with a free hydroxyl group in the C-4 position. Glycosylation of 13 with acetobromomannose (8), followed by debenzylation, deacetylation, and hydrazidation, gave 8-(hydrazinocarbonyl)octyl 4-O-α-D-mannopyranosyl-α-D-mannopyranoside (1). Total yield of 1 from 10 was 25.1%. Tritylation of 10, followed by acetylation and detritylation, gave a glycosyl acceptor (18) with a free hydroxyl group in the C-6 position. Analogous condensation of 18 with 8, followed by deacetylation and hydrazidation, gave 8-(hydrazinocarbonyl)octyl 6-O-α-D-mannopyranosyl-α-D-mannopyranoside (2). Total yield of 2 from 10 was 22.9%. These mannose dimers were coupled to BSA by the acyl azide method. Using the antibodies against the mannose dimers, an enzyme linked immunosorbent assay (ELISA) was established to measure the small amount of mannose dimers coupled to proteins. These two neoglycoproteins appeared to inhibit the antigen-specific human T cell proliferation over 100 fold more efficiently than free mannose dimers.     

Aqueous chromatography system using pH- and temperature-responsive stationary phase with ion-exchange groups

We report on the development of a novel analytical HPLC technique of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, ketoprofen and naproxen, with an isocratic aqueous mobile phase. In this study, we designed a new pH- and temperature-responsive copolymer of N-isopropylacrylamide (NIPAAm), butyl methacrylate (BMA) and N,N-dimethylaminopropylacrylamide (DMAPAAm). The copolymer was modified with cross-linked poly(NIPAAm-co-BMA-co-DMAPAAm) (IBD) hydrogel on to aminopropyl silica beads, and the products were evaluated as HPLC packing materials for an ion-exchange- and temperature-responsive chromatography. The property of the surface of the stationary phase was altered from hydrophilic to hydrophobic, and from charged to non-charged by changes in the temperature and pH. In addition, it is possible that ion-exchange groups can appear or be hidden on the polymer chain surface by temperature changes. The interactions of NSAIDs with this stationary phase were controlled by the temperature and the pH with a constant aqueous mobile phase. PH- and temperature-responsive chromatography is expected to be useful for the separation of pharmaceuticals and biomolecules.     

An iridoid glucoside dimer and a non-glycosidic iridoid from the leaves of Lasianthus wallichii

A new iridoid glucoside dimer (1) and a non-glycosidic iridoid (2) was isolated together with the known compounds, asperuloside (3), paederoside (4), daphylloside (5), citroside A (6) and benzyl 6-O-alpha-L-rhamnopyranosyl-beta-D-glucopyranoside (7), from the leaves of Lasianthus wallichii. The structures of the new compounds were elucidated by spectroscopic and chemical evidence.