Michihiko Ochiai

A new 1,3-dipolar cycloaddition reaction : Synthesis of some isoxazolidine derivatives

Abstract A new 1,3-dipolar cycloaddition reaction with formaldoxime as a 1,3-dipole compound has been discovered. Stereospecificity of the reaction and mass spectral data are discussed. With ethyl propiolate, 3,5-diethoxycarbonylpyridine, formed via a 1,4-dipolar cycloaddition reaction, was obtained.

Electrochemical reduction of cephalosporanic acids

Electrochemical reduction of cephalosporanic acid derivatives (I) bearing various substituents at the 3-position gave the corresponding 3-methylenecepham derivatives (II), a new class of cephalosporins. Reductive opening of the 3-hydroxymethyl-3-cephem-4-carboxylic acid lactone (IV) was effected to give (II) by cathodic reaction. The 3-methylenecepham derivatives (II) were readily isomerized to the 3-methyl-3-cephem derivatives (III) providing a new synthesis of cephalexin [7-(D-2-amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid](IIIc). The reaction mechanism is discussed on the basis of deuteriation and polarography of the cephalosporins involved.

An efficient synthesis of a key intermediate for optically active 5,6-cis-carbapenem antibiotics

Abstract A versatile intermediate (18) for optically active 5,6- cis -carbapenem antibiotics was synthesized with a highly regioselective intramolecular aldol condensation as a key step.

A novel photo-induced methylation of pyrimidines and condensed pyrimidines☆

Abstract A new photo-induced methylation of pyrimidines and condensed pyrimidines by irradiating an acidic solution of the bases in methanol is described. The scope and limitation, effects of acids, the calculation of the reactivity indices by the MO method, effect of bases on ·CH2OH radical formation, and the reaction mechanism are discussed.

Synthesis of lactivicin analogues

Abstract Aza analogues of lactivicin (1), a recently discovered novel antibiotic, were prepared by an application of our earlier convenient synthesis of 1 and its derivatives. A 1-unsubstituted pyrazolidinone derivative bearing 2-aminothiazol-4-yl-(Z)-methoxyiminoacetyl group exhibited in vitro antibacterial activity.

Synthesis of γ-lactam analogues of carbapenems with substituted-thio groups at the C-3 position

γ-Lactamanalogues of carbapenems{(7S)-7-acylamino-2-carboxy-3-(substituted-thio)-1-azabicyclo[3.3.0]oct-2-en-8-ones}(2) were synthesized starting from L-aspartic acid. Condensation of the oxo ester (4) with 2, 4-dimethoxybenzylamine followed by cyclization gave preferentially the E-γ-lactam (6), which was transformed into the 3, 5-cis-5-carboxymethyl-γ-lactam cis-(9)via stereoselective catalytic reduction. The major product cis-(9) and its trans-isomer were converted into compound (2)via a carbene insertion reaction. The antibacterial activity of the trans-acetamidoethylthio derivative (23) slightly exceeded that of the corresponding cis-derivative (17).

SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF 7β-[2-(2-AMINOTHIAZOL-4-YL)ACETAMIDO]CEPHALOSPORIN DERIVATIVES

In an effort to improve the antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]-cephalosporins by introducing a methoxyimino group into the 7-acyl side chain, geometrically isomeric 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acids and their derivatives were selectively synthesized. Structurally related acid derivatives were also synthesized. A facile and practical synthesis of an important starting material, 2-(2-chloroacetamidothiazol-4-yl)-(Z)-2-methoxyiminoacetic acid, for the preparation of SCE-1365 which is now under extensive clinical trial was achieved.

A facile one-step synthesis of adenine

Abstract A facile one-step synthesis of adenine has been achieved by the reaction of formamide with POCl 3 in a sealed tube. A maximum yield reached 43·5% of theory calculated on formamide under optimal conditions. Hydrogen cyanide is not considered a possible intermediate for the formation of adenine because H 14 CN added to the reaction mixture is not incorporated. A speculative mechanism for the reaction is proposed.

Synthesis of lactivicin and its derivatives

Lactivicin, a new type of antibiotic having β-lactam-like activity, and its derivatives were synthesized starting from 4-benzyloxycarbonylamino-3-isoxazolidinones and 2-oxoglutaric acid.

Reduction of cephalosporanic acids with chromium(II) salts : Synthesis of 3-methylenecepham derivatives☆

Abstract 7-Acylaminocephalosporanic acid derivatives (1) were converted into 7-acylamino-3-methylenecepham-4-carboxylic acids (2) by treatment with chromium(II) salts in aqueous media. The esters (4a or 4b) of 7-acylamino-3-methylenecepham compounds were readily isomerized to the 3-methyl-3-cephem compounds (5a or 5b) under basic conditions. The reaction mechanism is discussed.