During the past several years, mass spectrometry has made great progress in the analytical field of biological molecules. The progress has been mainly achieved with the development of new soft ionization techniques, such as plasma desorption, laser desorption, molecular secondary ion mass spectrometry, and fast atom bombardment mass spectrometry, and with the development of a big mass spectrometer. It has been demonstrated that polar nonvolatile big bioorganic molecules can be ionized without dissociation by soft ionization methods, which are called desorption ionization. The soft ionization methods and recent applications are overviewed. Newly developed thermospray ionization seems to be obtaining a reputation as a suitable ionization method for LC/MS and several applications have been achieved more recently. The application of tandem mass spectrometry (MS/MS) to structure analysis or mixture analysis of bioorganic samples has started recently, while it was widely used as a method for analyzing the ion structure of small molecules. These combination techniques of using a mass spectrometer with a liquid chromatograph or another mass spectrometer are promising methods for mixture analysis and they are also reviewed here.
Fast atom bombardment mass spectrometry (FAB/MS) is one of the most successful soft ionization methods for MS analysis of nonvolatile, thermolabile, polar organic compounds. The ionization occurs as a sputtering process caused by impact of the activated fast atom beam on the sample which is generally dissolved in a viscous liquid such as glycerol. The minimun amount of the sample to obtain a good spectrum is usually 0.1 to 1.0 μg and the mass spectrum lasts 10 to 30 minutes. The sophisticated mass spectral techniques such as MS/MS and HR/MS can be successfully adapted to the FAB ionization to analyze complicated organic mixtures as well as biological samples. The ionization source and the ionization process, types of liquid matrices and their roles, instruments, linked scan, HR/MS for FAB/MS and their applications for organic and biological research areas are discussed.
Reaction of alkyl diazoacetate with an olefin catalyzed by a chiral copper complex gives an optically active alkyl cyclopropanecarboxylate. This chiral copper carbenoid reaction was successfully applied to the synthesis of industrially valuable cyclopropanecarboxylic acids : (+) -trans-chrysanthemic acid, (+) -cis-permethrinic acid and (+) -2, 2-dimethylcyclopropanecarboxylic acid. A series of effective catalysts, chiral Schiff base-copper complexes, was prepared starting with an optically active α-amino acid to achieve more than 90 % e.e. of the products. The chirality of the products was correlated with that of the catalyst on the basis of metallacyclobutane intermediates.
1-Phenylethylamine was resolved into a pair of enantiomers by preferential crystallization of its cinnamic acid salt. A working hypothesis was proposed for the transformation of racemates into racemic mixtures (conglomerates) on the basis of structural correlation between 1-phenylethylamine and an achiral acid used. The validity of the hypothesis was verified by the success in the optical resolution of 1-phenyl-2- (p-tolyl) ethylamine, 1- (4-isopropylphenyl) ethylamine, 2- (anilinomethyl) - pyrrolidine, and 2-endo-benzamido-5-norbornene-1-endo-carboxylic acid by preferential crystallizations. erythro-2-Amino-1, 2-diphenylethanol was also resolved by preferential crystallization of its cinnamic acid salt and applied as a chiral auxiliary in the optical resolution of racemic acids, the enantioselective reduction of ketones, and the alkylation of ketones and acids. Optically active anti head-to-head coumarin dimer was obtained by the fractional crystallization of the diasteromeric diamides with 1-phenylethylamine. Optically active polyamides were prepared from the dimer and diamines and found to be useful as a chiral stationary phases for HPLC.
Aliphatic carbonates are easily synthesized from alkyl halides, alcohols, sodium carbonate and carbon dioxide in the presence of the catalyst. This method is characteristic at the points of one pass route for the mixed dialkyl carbonates (ROCO2R') and the new process using no toxic phosgen. Diethylene glycol bis-allyl carbonate (DEG-BAC), which is used mainly for the ophthalmic eye glasses, has been produced by the “phosgen process”. We applied the “sodium carbonate process” to DEG-BAC and established the new industrial process for the production.
The preparation of a new polyphosphate reagent, trimethylsilyl polyphosphate (polyphosphoric acid trimethylsilyl ester) (PPSE), and its use in organic synthesis are described. PPSE is essentially aprotic and soluble in organic solvents and activates oxygen functions under mild conditions for preparative transformations. Some synthetically useful reactions promoted by PPSE are exemplified.