Ankerfarm, S.p.a.

Glaxo Group Limited

Gino Cotti

Marco Croci

Renato Broggi

A process is provided for preparing alpha-6-deoxytetracyclines depicted by the formula: ##STR1## wherein Y is H, F, Cl, Br or I; and R is H, OH or --O--CO--(C.sub.1-6 alkyl); which comprises: contacting a 6-demethyl-6-deoxy-6-methylene tetracycline or salt thereof having the formula ##STR2## in which Y and R are as given above, with hydrogen at a temperature of between 15.degree. C. and 80.degree. C. in the presence of a catalyst soluble in a polar solvent, said catalyst being a complex of rhodium with electron donor ligands of a tertiary phosphine selected from the group consisting of triphenylphosphine, tributylphosphine, triethylphosphine, diethylphenylphosphine and diphenylethylphosphine and said polar solvent being a mono- or polyhydric alcohol with from 1 to 4 carbon atoms, N,N-dimethylformamide, N,N-dimethylacetamide, dioxan, tetrahydrofuran, methoxyethanol, ethoxyethanol, acetonitrile or pyridine.

Process for the preparatin of .alpha.-6-deoxytetracyclines

A process for preparing semi-synthetic penicillin antibiotics, especially ampicillin, is disclosed which comprises acylating a silylated 6-aminopenicillanic acid in the presence of primary or secondary carboxamide bases as hydrogen halide acceptors. The products may be obtained in good yield and high purity and the amount of toxic contaminants in the products is significantly reduced, thus substantially eliminating unpleasant side-effects.

Manufacture of semi-synthetic penicillin antibiotics

A process for preparing semi-synthetic penicillin antibiotics, especially ampicillin, is disclosed which comprises silylating 6-aminopenicillanic acid using a silylating agent which generates a primary or secondary carboxamide base, and then acylating the silylated 6-aminopenicillanic acid in situ using the primary or secondary carboxamide base as hydrogen halide acceptor. No further base needs to be added, and the products may be obtained in good yield and high purity with the amount of toxic contaminants in the products significantly reduced. Unpleasant side-effects may thus be substantially eliminated.

This invention relates to a novel water soluble derivatives of 6-deoxy-tetracyclines, particularly of doxycycline, in which a methionine group is linked to the tetracycline group through a methylene bridge, thus obtaining a derivative which is not only water soluble at neutral pH, but also endowed with outstanding properties from the point of view of the therapeutical use.

Water-soluble derivative of 6-deoxy-tetracyclines

The invention relates to the preparation of 6-demethyl-6-deoxy-6-methylene-tetracycline by means of reductive dehalogenation of the corresponding 11a-halo-6-demethyl-6-deoxy-6-methylene-tetracycline, the reaction being carried out in presence of the stoichiometric quantity of a tertiary phosphine, arsine or stibine and in a polar solvent. The time and temperature of the reaction are controlled within specified limits to obtain a complete conversion.

Process for the preparation of

This invention relates to a process for the preparation of .alpha.-6-deoxytetracyclines, by the simultaneous reductive dehalogenation and reduction by hydrogen, in a polar solvent of the corresponding 11a-halo-6-demethyl-6-deoxy-6-methylene-tetracycline, in presence of a suitable member of the group of the tertiary phosphines, arsines and stibines, as regards the dehalogenation and of a catalyst, selected from amongst the complexes of noble metals with electron-donor ligands, soluble in the reaction medium, whereby the reaction is carried out according to the mechanism of the homogeneous catalysis.

Growing community of inventors

Monza, Italy

Gino Cotti