Methodology for the rapid separation of gentamicin components and regiospecific synthesis of gentamicin conjugates

摘要

An efficient synthesis of a single conjugate of gentamicin is described. Reaction of the primarily three component gentamicin complex with excess benzyl chloroformate provided a mixture of the amine-protected components which were separable at scale by preparative HPLC using UV detection. Mild deprotection provided the pure separated components. Conjugation of one deprotected component permitted preparation of a single, manufacturable gentamicin conjugate. These strategies provide a general method for the separation of gentamicin components as well as a useful solution for the regiospecific synthesis of gentamicin conjugates.