- Silylation process
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A process for the silylation of 6-aminopenicillanic acid or 7-amino-desacetoxy-cephalosporanic acid by silylation in certain carboxylic acid esters and its use in the production of 6-alpha-aminoacyl-penicillins and 7-alpha-aminoacyl-desacetoxy-cephalosporins.
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- Beta lactam production
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A new process is described for the production of 6-alpha-amino-penicillins and 7-alpha-amino-desacetoxy-cephalosporins free from halogen-containing solvents by acylating 6-APA, 7-ADCA or a derivative thereof in a halogen-free solvent.
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- Pharmaceutical tablet, pharmaceutical granulate and process for their preparation
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A pharmaceutical tablet containing an amphoteric beta-lactam antibiotic, microcrystalline or micro fine cellulose or a mixture of both and a second disintegrant, being low-substituted hydroxypropylcellulose, which fully disintegrates in water within 60 seconds. When swallowed it shows a bioavailability as good as a pharmacy prepared suspension of the antibiotic. The tablet is compressed from a mixture containing a new granulate which is prepared from the antibiotic substance, microcrystalline and/or micro fine cellulose and water only. Such tablets can also be prepared by using other known tablet disintegrants as the second disintegrant.
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- Manufacture of semi-synthetic penicillin antibiotics
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Improvements in or relating to the manufacture of semi-synthetic penicillin antibiotics are described. More particularly an improved process for the preparation of a 6β-acylamino penicillanic acid antibiotic product is described in which 6β-aminopenicillanic acid (6-APA) is reacted in an inert solvent with a silylating agent to form a silylated compound of formula (I) STR1 wherein R1 represents a hydrogen atom or a tri(C1-6 alkyl)silyl group, and R2 represents a tri(C1-6 alkyl)silyl group and the compound of formula (I) is thereafter contacted with an acyl chloride or protected acyl chloride corresponding to the desired 6β-acylamino group, the silyl groups are cleaved and the desired antibiotic product is recovered, silylation being effected using a tri(C1-6 alkyl) silylurea or tri(C1-6 alkyl) halosilane and the compound of formula (I) produced being reacted without intermediate isolation with the acyl chloride or protected acyl chloride, wherein acylation is effected in the presence of a hydrogen halide acceptor mixture comprising in excess of 0.15 and preferably up to 3.00 moles of urea per mole of 6-APA; in excess of 0.15, and preferably up to 1.30 moles of bis-tri-(C1-6 alkyl)silylurea per mole of 6-APA; and in excess of 0.25, and preferably up to 3.30 moles of tri-(C1-6 alkyl)-ammonium halide per mole of 6-APA. The process is especially useful for the preparation of ampicillin and amoxycillin in high yield and high purity.
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- Method for synthesis of penicillin
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This invention relates to a method for synthesizing a penicillin by reacting a silylate of 6-aminopenicillanic acid and a carboxylic acid halide in the presence of an insoluble weakly basic resin having a three-dimensional structure.
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- Process for preparing β-lactam antibiotics
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Compounds of formula (I): STR1 [in which: Z represents a group of formula STR2 R represents a hydrogen atom, a 1-pyridyl group or a group of formula --YR' (in which: R' represents an alkyl group, an alkanoyl group a carbamoyl group or a heterocyclic group; and Y represents an oxygen or a sulphur atom); X represents a hydrogen atom or a hydroxy group; and the α-amino acid moiety is in the D(-) configuration] are prepared by silylating the corresponding compound having an amino group at the 6-penam or 7-cepham position, acylating the silylated compound with D(-)-p-hydroxyphenglycyl chloride hydrochloride or D(-)-p-hydroxyphenylglycyl chloride hydrochloride and then hydrolyzing the acylated product. By carrying out the reaction in the presence of an N-alkylpyrrolidone, it is possible to improve the yields and purity of the desired product.
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- Process for the preparation of phosphorus derivatives of secondary ammonium salts of penam and cephem compounds
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An improvement in the conversion of penam and cephem compounds to secondary ammonium salts of phosphite amides thereof by reacting as follows: STR1 wherein --R, is the non-reacting balance of the penam or cephem compound and STR2 ARE NON-REACTING SUBSTITUENTS. Catalytic amounts of H--N or the hydrogenhalide thereof may be present in the reaction medium.
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- Antibiotics
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A new anhydrous form of ampicillin is described. The new form is stable and relatively highly soluble, and may be prepared by heating ampicillin trihydrate rapidly to a temperature of above about 100°C, for example by contact with a hot water-immiscible liquid.
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