Akira Morimoto

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.

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.

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.

Lycopodium Triterpenoids. (8). The Structures of Lycoclavanin, a Triterpenoid-tetraol Possessing Conjugated Ketone Chromophor, and a New Tetraol, Lyclaninol

Lycoclavanin, a Lycopodium triterpenoid containing four hydroxy-groups and a conjugated ketone, was established as 16-oxoserrat-14-ene-3α, 20β, 21β, 24-tetraol (7a) by spectral and chemical means. Correlations of lycoclavanin with 16-oxo-lycoclavanol (6a) and with serratenediol (17a) were described. A new tetraol occurring in L. clavatum was also established as serrat-14-ene-3α, 20β, 21β, 24-tetraol (23a).

Intralesional Injection of Absolute Alcohol Into Symptomatic Vertebral Hemangiomas: A Case Report and Review of the Literature

The management of vertebral hemangiomas remains controversial. This report describes the successful management of spinal cord compression caused by an intraosseous and extraosseous vertebral hemangioma with the percutaneous injection of absolute alcohol. A 71-year-old woman presented with lower extremity weakness and sensory disturbance. Magnetic resonance imaging and computed tomography (CT) confirmed the presence of a vertebral hemangioma involving the Th11 vertebral body. A CT-guided percutaneous transpedicular injection of absolute alcohol into the affected vertebral body resulted in symptomatic and imaging improvement. CT-guided percutaneous transpedicular injection of absolute alcohol into symptomatic vertebral hemangiomas is a simple, safe, and effective technique for relieving compression and devascularizing the hemangioma.

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

Cephalosporanic acid derivatives (I) were converted into 3-methylenecepham derivatives (II) on treatment with chromium(II) salts in aqueous media, and esters of 3-methylenecepham derivatives were readily isomerized to the 3-methyl-3-cephem derivatives (VII) under basic conditions.

Nucleophilic displacement reactions of 3,6-dichloropyridazine 1-oxide with sulphur nucleophiles

The displacement reaction of 3,6-dichloropyridazine 1-oxide with sodium sulphide took place at the 6-position to give 3-chloropyridazine-6-thiol 1-oxide, in contrast to the results with oxygen and nitrogen nucleophiles. Other sulphur nucleophiles (thiourea and phenylmethanethiol) also reacted at the 6-position; this is inconsistent with a previously reported reaction with potassium methanethiolate.

A method for the preparation of 7?-methoxycephalosporins

A method for the preparation of 7α-methoxycephalosporins has been developed. 7β-Phosphoramidodeacetoxycephalosporin (6) and 7β-phosphoramidocephalosporin (14) obtained from the 7β-amino-derivatives (5) and (13), were converted into 7α-methoxy-7β-phosphoramidodeacetoxycephalosporin (7) and 7α-methoxy-7β-phosphoramidocephalosporin (15), respectively, by reaction with LiOMe and ButOCl. Treatment of (7) with BunLi and Et3N followed by acylation with phenylacetyl chloride gave 7α-methoxy-7β-phenylketenimino-derivative (11), which were easily hydrated to 7α-methoxy-7β-(phenylacetamido)deacetoxycephalosporin (12). Treatment of (15) under similar conditions afforded, contrary to the result obtained with (7), 7α-methoxy-7β-(phenylacetamido)cephalosporin (16), without any of the corresponding ketenimine. This method was also successfully applied to the synthesis of 6α-methoxypenicillins.