MICROSCOPIC PROTONATION CONSTANTS IN TOBRAMYCIN AN NMR AND PH STUDY WITH THE AID OF PARTIALLY N-ACETYLATED DERIVATIVES

Three tetra-N-acetyl derivatives and one tri-N-acetyl derivative of tobramycin (1) have been prepared by partial N-acetylation. Comparison of the pK(a) values, determined by NMR chemical shift titrations and pH titration of the derivatives, with those of unprotected 1 suggests that protonation equilibria at any particular amino group in 1 are not likely to be influenced by those at other sites. pH-Dependent conformational changes in 1 were assessed on the basis of H-1 and C-13 chemical shift changes in the derivatives.