Application of molecular-secondary-ion mass spectrometry for drug metabolism studies. I. Direct analysis of conjugates by thin-layer chromatography-secondary-ion mass spectrometry

Molecular-secondary-ion mass spectrometry (SIMS) is a suitable method for the analysis of nonvolatile substances such as conjugated metabolites of drugs. We have developed a simple method for the direct SIMS measurement of conjugates following thin-layer chromatography without any extraction procedure. After separation with a butanol-acetic acid-ethanol-water (3:1:1:1, v/v) system, the spot was cut out and attached to a SIMS probe. The conjugates of p-nitrophenol and 4-hydroxyantipyrine were measured. The quantitative application of the method is also discussed, using deuterium-labelled internal standards for p-nitrophenol conjugates.     

Stereocontrolled synthesis of 8,11-dideoxytetrodotoxin, an unnatural analogue of puffer fish toxin

8,11-Dideoxytetrodotoxin, an unnatural tetrodotoxin analogue, was synthesized in a highly stereoselective manner from a common intermediate from our synthetic studies on tetrodotoxin. The key features in the synthesis were as follows: neighboring group participation of a trichloroacetamide to allow regioselective and stereoselective hydroxylation, protection of a delta-hydroxylactone as an ortho ester, and guanidine installation through the use of Boc-protected isothiourea. Global deprotection of the fully protected intermediate under acidic conditions gave 8,11-dideoxytetrodotoxin, which exhibited very weak biological activities.     

Photochromism of dinaphthylethene derivatives. Stability of the closed-ring forms

Stability of various types of closed-ring forms of dinaphthylperfluorocyclopentenes was investigated from both experimental as well as theoretical points of view. The stability was dependent on the energy differences between the open-ring and the closed-ring forms. When the energy difference was small, the closed-ring form became stabler.     

beta-Isocupreidine-catalyzed asymmetric Baylis-Hillman reaction of imines

[reaction: see text] beta-Isocupreidine (beta-ICD)-catalyzed asymmetric Baylis-Hillman reactions of aromatic imines with 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) give (S)-enriched N-protected-alpha-methylene-beta-amino acid esters. In contrast to the corresponding aldehydes, imines show the opposite enantioselectivity. A mechanistic proposal governed by hydrogen bonding is presented.     

Oxidative rearrangement of cyclic tertiary allylic alcohols with IBX in DMSO

A practical and environmentally friendly method for oxidative rearrangement of five- and six-membered cyclic tertiary allylic alcohols to beta-disubstituted alpha,beta-unsaturated ketones by the IBX/DMSO reagent system is described. Several conventional protecting groups (e.g., Ac, MOM, and TBDPS) are compatible under the reaction conditions prescribed.     

Vinylhydroquinone. III. Copolymerization of vinylhydroquinone and vinyl monomers by tri-n-butylborane

The copolymerization of vinylhydroquinone (VHQ) and vinyl monomers, e.g., methyl methacrylate (MMA), 4-vinyl-pyridine (4VP), acrylamide (AA), and vinyl acetate (VAc), by tri-n-butylborane (TBB) was investigated in cyclohexanone at 30°C under nitrogen. VHQ is assumed to copolymerize with MMA, 4VP, and AA by vinyl polymerization. The following monomer reactivity ratios were obtained (VHQ = M₂): for MMA/VHQ/TBB, r₁ = 0.62, r₂ = 0.17; for 4VP/VHQ/TBB, r₁ = 0.57, r₂ = 0.05; for AA/VHQ/TBB, r₁ = 0.35, r₂ = 0.08. The Q and e values of VHQ were estimated on the basis of these reactivity ratios as Q = 1.4 and e = ?;1.1, which are similar to those of styrene. This suggests that VHQ behaves like styrene rather than as an inhibitor in the TBB-initiated copolymerization. No homopolymerization was observed either under nitrogen or in the presence of oxygen. The reaction mechanism is discussed.     

A Formal Total Synthesis of Taxol Aided by an Automated Synthesizer

A 36‐step synthesis was carried out in automated synthesizers to provide a synthetic key intermediate of taxol. A key step involved a microwave‐assisted alkylation reaction to construct the ABC ring system from an AC precursor. Subsequent formation of the D ring afforded baccatin III, a well‐known precursor of taxol.     

Preparation of macroreticular redox resins with hydroquinone and catechol units as pendant groups and their properties

Macroreticular redox resins with hydroquinone and catechol units as pendant groups were prepared by the Friedel-Crafts reaction of macroreticular styrene/divinylbenzene copolymer with 2,5- and 3,4-dimethoxybenzyl chlorides, followed by removal of the methyl groups with hydrobromic acid. The redox capacity of the macroreticular resins was determined by oxidation of hydrazobenzene with resins in oxidized form. Resins with 1,4-benzoquinone units were capable of oxidizing hydrazobenzene, whereas those with 1,2-benzoquinone (catechol quinone) units exhibited no apparent oxidative ability; this seems to be due to a complex formation between azobenzene and the catechol units in the reduced resins. Adsorption of metallic ions onto catechol-containing resins showed a high selectivity for Hg²⁺ ion. The effects of pH, reaction time, and ion concentration on the adsorption were also studied.     

Photo-oxidation-reduction sensitized by copolymers of [2-(9,10-anthraquinonyl)]methyl methacrylate

Copolymers of [2-(9,10-anthraquinonyl)]methyl methacrylate (AQMMA) with (2-naphthyl)-methyl methacrylate (NMMA) and benzyl methacrylate (BMA) were prepared. The photo-sensitizing efficiencies of these polymers for the oxidation-reduction of l-ascorbic acid and Fast Red A were examined in dimethylformamide. AQMMA-BMA copolymers with 6 and 14 mole% of AQMMA afforded nearly equal quantum yields, 1.6 times as large as that of a low molecular model compound, [2-(9,10-anthraquinonyl)]methyl acetate (AQMAc). The observed increase in the quantum yield is discussed in terms of energy delocalization, decreased rate of diffusion and cage effect by polymer segments. AQMMA-BMA-NMMA copolymers gave decreased quantum yields owing to intramolecular quenching of the anthraquinone triplet by the naphthalene unit. The intramolecular quenching was interpreted according to Perrin's model of static quenching. With the radius of quenching sphere assumed to be 13 A, the local naphthalene concentration around the anthraquinone unit was suggested to be approximately 20 times as small as that in solid films.     

High-efficiency and minimum-waste continuous kinetic resolution of racemic alcohols by using lipase in supercritical carbon dioxide

A novel continuous-flow scCO(2) process for kinetic resolution of racemic alcohols can be performed with an immobilized lipase to lead to a quantitative mixture of the corresponding optically active acetates with up to 99% ee and unreacted alcohols with up to 99% ee, in which the productivity of the optically active compounds was improved by over 400 times compared to the corresponding batch reaction using scCO(2).