Progress toward the total synthesis of ciguatoxins: a convergent synthesis of the FGHIJKLM ring fragment

[structure: see text] A highly convergent synthetic route to the FGHIJKLM ring fragment of ciguatoxins has been developed, which relied on extensive use of the B-alkyl Suzuki-Miyaura coupling reaction.     

Ruthenium-catalyzed one-pot hydroformylation of alkenes using carbon dioxide as a reactant

A new hydroformylation of alkenes using carbon dioxide as a reactant is shown to take place in the presence of ruthenium cluster complexes and halide salts. Similar or even better yields of alcohols were formed as compared to the conventional hydroformylation with CO under the same reaction conditions. The reaction proceeded in three steps: CO₂ is first converted to CO; then it is used as a reagent for hydroformylation to give aldehyde; subsequently, it is hydrogenated to alcohol. ESI-mass spectrometric analyses of the reaction solutions indicated formation of four kinds of ruthenium anionic complexes including tetra-, tri-, and mononuclear species. On the basis of experimental findings, possible roles of these complexes are discussed.     

Application of samarium diiodide (SmI2)-induced reduction of gamma-acetoxy-alpha,beta-enoates with alpha-specific kinetic electrophilic trapping for the synthesis of amino acid derivatives

Gamma-acetoxy-alpha,beta-enoates were easily reduced by samarium diiodide (SmI2) in THF to generate samarium dienolates which were kinetically trapped with ease at their alpha-positions by electrophiles (proton, aldehydes or ketones) to yield (E)-alkene dipeptide isosteres or gamma-amino acid derivatives in high chemical yields.     

Elucidation of solid-state complexation in ground mixtures of cholic acid and guest compounds

The solid-state complexation between cholic acid (CA) and either methyl p-hydroxybenzoate (MPB) or ibuprofen (IBP) was investigated. Powder X-ray diffractometry, IR spectroscopy and thermal analysis suggested the complex formation between CA and MPB as well as between CA and IBP by co-grinding method. The stoichiometry of CA-MPB was 1 : 1 while that of CA-IBP was 2 : 1, reflecting the effect of guest size on complex formation. The guest compounds were assumed to be included in the channel of complexes formed by hydrogen bonds among CA molecules.     

The use of ozone as the primary digestion reagent for the cold vapor mercury procedure

Ozone was tested as an alternative digestion/oxidation system to the permanganate/peroxidisulfate currently used in the cold vapor mercury method. The results indicate that the digestion of comparable size samples to the 'Standard Method' was complete in less than 2 min. A 0.5 ml (10 ppb) sample size was completely oxidized in less than 30 s. The batch system used produced a limit of detection (LOD) for mercury(II) chloride, methylmercury chloride, and phenylmercury acetate of about 0.5 ppb.     

SmI2-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates with application to the synthesis of functionalized (Z)-fluoroalkene-type dipeptide isosteres

A samarium diiodide (SmI(2))-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates (15, 29, and 34) was successfully applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres (23, 30, and 35), which have served as potential dipeptide mimetics. Reduction of the gamma,gamma-difluoro-alpha,beta-enoates by SmI(2) proceeded via successive two-electron transfers to form dienolate species which upon kinetically controlled trapping with t-BuOH yielded Xaa-Gly-type fluoroalkene isosteres exemplified by 23, 30, and 35. Replacement of the t-BuOH kinetic trapping agent with aldehydes or ketones provided access to alpha-substituted fluoroalkene isosteres (43 and 45) through aldol reactions of Sm-dienolates with the carbonyl compounds. Of particular note, the use of the SmI(2)-HCHO reagent system with chiral enoate 34 provided D-Phe-psi[(Z)-CF[double bond]CH]-D/L-Ser isosteres (45), which could be converted to enantiomerically pure isosteres (49-52) that bore a variety of side chain functionalities at the alpha-position. This was achieved by a sequence of manipulations consisting of beta-lactone formation followed by chromatographic separation and ring-opening with soft nucleophiles. Included in the present work is the first utilization of a Rh-catalyzed Reformatsky reaction of chiral imines for the stereoselective preparation of alpha,alpha-difluoro-beta-amino acid derivatives (28 and 33). The appropriate choice of reagents (carbonyl compounds for kinetic trapping or ring-opening nucleophiles and imines for Reformatsky reactions) allows the presented methodology to yield various fluoroalkene isosteres possessing a wide range of side chain functionalities.     

A new synthetic pathway of segmented tri-block copolyether

A new synthetic pathway of A–B–A tri-block copolyether which is composed of a hydrophilic poly(oxyethylene) unit as an A part and a hydrophobic poly(oxy-2-methyl-trimethylene) unit as a B part is proposed. Telechelic α-tosyl-ω-tosyloxypoly(oxy-2-methyl-trimethylene) derived from tosylation of poly(oxy-2-methyl-trimethylene glycol) (PMTG) was allowed to react with poly(ethylene glycol) (PEG) in the presence of sodium hydroxide. T_g of the resulting A–B–A tri-block copolyether (PEMG) (M?_n = 1600) was ?72°C and its specific gravity [D₄¹⁵] was 1.055.     

Purification of enzymes by high-speed gel filtration on TSK-GEL SW columns

The purification of enzymes was investigated by high-speed gel filtration on TSK-GEL G3000SWG columns packed with porous silica gel deactivated by chemically bonded hydrophilic compounds. Crude β-galactosidase from bacterial cells and commercial urease were purified ca. 15-fold in a single gel filtration. These enzymes were eluted within an hour from the column and the recoveries of enzymatic activity were almost 100% although the operation was carried out at room temperature (22°). Samples up to 100 mg could be applied to the column without loss of separation efficiency.     

Parallel synthesis of tandem Ugi/Diels-Alder reaction products on a soluble polymer support directed toward split-pool realization of a small molecule library

A series of parallel reactions were carried out for the tandem Ugi/Diels-Alder reaction on our MPEG-O-CH₂- platform. Ninety-six out of a 100 entries were successful to give complex heterotricycles. The stereoselectivity was found not to be influenced by the building blocks used for amine and carboxylic acid components. An unexpected side pathway was found but was suppressed by employing appropriate reaction conditions. The reaction was also performed on solid phase, by which a larger library is potentially realized by employing the split-pool method.