| 摘要 |
The invention relates to 6-deoxy- or 6-deoxy-6-demethyl tetracycline derivatives containing a 7 and/or 9 amino group in which at least one of said amino groups is substituted by one or two radicals of the formula <FORM:1003474/C2/1> in which R3 and R4 are the same or different and are hydrogen atoms, alkyl groups containing up to 6 carbon atoms or aryl or aralkyl groups. These tetracycline derivatives are prepared by an appropriate method from the following (a) condensing the corresponding tetracycline having a 7 and/or 9 amino group, wherein the amino group may be formed in situ by reduction of the corresponding substituted-tetracycline, wherein the substituent is a nitro, nitroso, diazonium halide, benzeneazo or substituted benzeneazo group, with one or two mols. of carbonyl compound per amino group on the tetracycline of the formula <FORM:1003474/C2/2> e.g. formaldehyde, for each mol. of tetracycline and separately or simultaneously reducing the resulting condensate e.g. with hydrogen and a catalyst such as Pd, Rh, Pt on an inert carrier, Ni or copper chromites, or formic acid; (b) reacting the corresponding 7 and/or 9 amino tetracycline with a formylating agent followed by reduction to the 7 and/or 9 methylamino tetracycline; (c) reacting the corresponding 7 and/or 9-amino tetracycline with an appropriate thioacylating agent e.g. with a dithio carboxylic acid ester or acylation followed by reaction with P2S5, followed by reduction with hydrogen/Raney nickel; (d) reacting the corresponding 7 and/or 9 amino tetracycline on the 4-benzyl dimethylamino quaternary salt with one or two mols. of an alkyl or an aralkyl halide, sulphonate or sulphate, the said aralkyl compounds being those containing the group aryl-CH2- as the aralkyl group followed if necessary with catalytic debenzylation; and (e) condensing the corresponding 7 and/or 9-amino tetracycline with formaldehyde and an appropriate aldehyde by a Mannich reaction followed by catalytic reduction and/or hydrogenolysis. The reductions referred to above may also be carried out with Zn, Sn or Fe and HCf and with metal couples. The compounds when administered orally or parenterally are effective against staphylococcus. |
