GB1155029A - 7-Amino-3-Desacetyloxymethyl-3-Formyl-Isocephalosporanic Acid compounds and process for their manufacture - Google Patents

Abstract

1,155,029. Isocephalosporanic acid derivatives and process for their preparation. R. B. WOODWARD. 30 Aug., 1966 [9 Dec., 1965], No. 24390/68. Divided out of 1,155,023. Headings C2A and C2C. Compounds of the formula in which R 0 represents a hydrogen atom or an acyl group and R a stands for hydrogen or the residue of an alcohol, may be obtained by treating a 4,4-disubstituted-3-acyl-α-diformylmethyl- 2 - oxo - 1 - azetidino - [3,2-d] - thiazolidine methane carboxylic acid ester of the formula wherein Ac is an acyl radical and X is the disubstituted carbon atom of the thiazolidine ring, with an acidic agent selected from inorganic oxygen-containing acids, strong organic oxygencontaining acids, boron trifluoride and complexes thereof and tin tetrachloride while splitting the 5-membered sulphur-nitrogen ring and forming the new 6-membered sulphur-nitrogen ring, and optionally converting esterified carboxyl groups in the products to free carboxyl groups. The reaction may be effected in the presence or absence of added solvents with cooling or at ambient or elevated temperatures, and optionally in a nitrogen atmosphere and/or in a closed vessel. A resulting mixture of isomers obtained by the process may be resolved by conventional methods, e.g. by fractional crystallization, adsorption chromatography, and a resulting racemate may be resolved into the antipodes, for example, by forming a mixture of diastereoisomeric salts with optically active salt-forming agents, breaking down the mixture into the diastereoisomeric salts and converting the isolated salts into the free compounds. Inorganic oxygen-containing acids are, for example, sulphuric, phosphoric and perchloric acids, and strong organic oxygencontaining acids are, for example, substituted lower (up to C 7 ) alkane carboxylic acids and strong organic sulphonic acids; aprotic Lewis acids of the boron trifluoride type include boron trifluoride and complexes thereof, e.g. with ether or hydrogen fluoride, as well as tin tetrachloride, and mixtures of acidic agents may be employed. The acyl group R o in the products may be introduced by treating the free amino compound with a suitable acid or acid chloride or anhydride, and substituent groups in the products may be modified by conventional methods.