| 摘要 |
<p>Water-soluble aminomethyl derivatives of tetracycline having a low content of epitetra-cycline are prepared by reacting 1 mole of tetracycline, 1 to 2 moles of formaldehyde and 1 mole of an aliphatic or aromatic amino-acid, or a compound havin the general Formula I <FORM:1107706/C2/1> wherein n represents an integer from 1 to 3 inclusive, in a a lower aliphatic alcohol of 1 to 8 carbon atoms inclusive (e.g. EtOH or MeOH) and in the presence of sufficient amount of tertiary organic base (e.g. triethylamine, trimethylamine or pyridine) to impart to the mixture a pH from 7.5 to 8.5 at a temperature of 10 DEG to 50 DEG C. for 5 to 15 mins. Novel tetracycline derivatives of the Formula II <FORM:1107706/C2/2> wherein n is as above defined are prepared when one of the reactants is the compound of general Formula I. The derivatives are precipitated from the reaction mixture by cooling and acidification to pH 4-5. Examples of compounds prepared by this Mannich reaction are 3 - (carboxymethyl - 1 - piperidino) -, 3 - (carboxy - 1 - piperidino) -, 4 - (carboxy - 1 - piperidino)- and 7-carboxypropylamino-methyltetra-cycline. The novel piperidino carboxylic acid tetracycline derivatives of general Formula II above may be formulated into pharmaceutical preparations also containing a pharmaceutically acceptable carrier, e.g. suppositories.</p> |
