Verfahren zur Herstellung von neuen pentacyklischen Verbindungen mit antiotischer Wirkung

1,193,288. 4,12-Aza-tetracyclines. CHINOIN GYOGYSZER ES VEGYESZETI TERMEKEK GYARA RT. 9 Aug., 1967 [9 Aug., 1966; 6 July, 1967], No. 36643/67. Heading C2A. The invention comprises 4,12-azatetracyclinium compounds of Formula I wherein X is H or CH 3 , Y is H or halogen and Z- is the anion of an acid; and the corresponding betaine salts of Formula II wherein X and Y have the above meanings. Compounds of Formula I are obtained by treating compounds of Formula V with an acid e.g. a sulphonic or hydrohalic acid at a pH not greater than 2À0 in an alkanol at a temperature of 110-140‹ C. If the tetracycline is used in the form of the hydrochloride, an alkyl ester of a sulphonic acid or 1,3 propane sultone may be used. Zinc chloride may be used as a catalyst. Betaines of Formula II are prepared by reacting compounds of Formula I with a base e.g. an alkali metal bicarbonate, ammonium bicarbonate, an alkali metal acetate or an organic base especially hexamethylene tetramine. Compound I is reformed by treating the betaine II with an acid. A typical compound is 4 - desdimethylamino - 5a,6 - anhydro - 6- demethyl - 7 - chloro - 12 - deoxy - [(N - dimethyl) - 4,12 - aza] - tetracyclinium benzene sulphonate. A pharmaceutical composition comprises a tetracycline antibiotic of Formula I or II and a carrier for oral, parenteral, rectal or topical administration.