Original Articles
Lower Toxic Derivatives of Antibiotics. V Effects of Substituents on the Toxicity of a N-Methanesulfonate Derivative
1962 Volume 15 Issue 2 Pages 73-74
Details
1962 Volume 15 Issue 2 Pages 73-74
It has previously been reported1) that although kanamycin-N-methanesulfonates show less toxicity, no lowering of toxicity is exhibited in case of the compounds of NH·CHX·SO3- where X is replaced by alkyl or aryl group. The significant differentation has appeared to be related to the hydrolytic mechanisms of N-methanesulfonic groups. Alternative mechanisms of hydrolysis of N-methanesulfonates have thus been presented to explain the dissimilarity in toxicity beween substituted and unsubstituted N-methanesulfonates. In the present paper we wish to call further attention on the effect of substituents on the toxicity of N-methanesulfonate derivative.
Studies have been made to prepare derivatives of a type K(NH2)2(NH·CHCH2X·SO3H)2, wherein X represents an electronegative atom or group and K represents the residual part resulted from removing of (NH2)1 from kanamycin molecule. It seemed likely that the system -NH·CHCH2X>·SO3- would have a possibility to form a somewhat stabilized chelate ring and therefore, C-S fission would proceed in preference to N-C fission; this corresponds to the mechanism (I) in a previous paper1), lowering of toxicity being expected. It has been found that the results are in agreement with the above speculation as shown in Table 1
These derivatives except the promo derivative (III) showed significant lowering of toxicity. This is probably due to the fact that the promine atom generally fails to form hydrogen bond.
