GB947601A — Tetracycline compounds and preparation thereof

USPTO Abstract

The invention relates to a complex of a 12a-deoxytetracycline compound of formula: <FORM:0947601/C2/1> <FORM:0947601/C2/2> wherein X is hydrogen, chloro or bromo, A is hydrogen or methyl, B is hydrogen or hydroxyl and D is hydrogen or dimethylamino, and a metal capable of forming a chelate therewith, wherein the molar ratio of metal to tetracycline is from 3:1 to 1:3. The complexes are prepared by adding the metal, in the form of a salt thereof, which is soluble in the solvent system employed for the reaction, to the 12a-deoxytetracycline compound. The invention also relates to a process of preparing a tetracycline compound corresponding to the 12a-deoxytetracycline compounds of Formula I and II in which the 12a-deoxytetracycline of Formula I or II is contacted with an oxidising substance which is oxygen gas, air, an N-oxides of a tertiary organic amine, hydrogen peroxide, a metal peroxide or an organic peracid in a reactioninert solvent, said 12a-deoxytetracycline being in the form of a complex, in the presence of a complex or in the presence of a metal salt capable of forming a metal complex as above. Specified oxidising agents are sodium, potassium or lithium peroxide; peracetic and perbenzoic acids and N-oxides of trialkylamines, dilower alkylaryl amines, dialkyl, aralkylamines, pyridines and lower alkyl pyridines or substituted derivatives of such N-oxides in which the substituent is halogen, alkoxy, hydroxy or nitro. Specified complex forming metals are Ce, Sr, Ba, Ca, Hn, V, Ti, Ni, Cr, Co, Cd, Hg, Zn, Pb, Sn, Pt, Pd and Ag, which are used in the form of salts such as the chloride, bromide, iodide, sulphate, acetate, nitrate phosphate, propionate, butyrate, citrate, salicylate, benzoate, lactate, ferricyanido nitrite, cyanide, thiocyanate, thiosulphate, hydroxide, bromate, iodate, tartrate and carbonate. When the tetracycline end product contains a 4-dimethylamino group the starting material and end product may be separated by contacting the reaction mixture with a cation exchange resin and as anion exchange resin in either order. The corresponding 4-epitetracyclines are also formed by the above process for preparing tetracyclines.