Chemistry of bleomycin. XVI. Epi-bleomycin.

Abstract

As previously reported1,2), migration of the carbamoyl group from the 3-to the 2-hydroxyl group of the mannose moiety of bleomycin occurs in aqueous alcoholic solution of copper-free bleomycin in the presence of a weak base such as triethylamine until an equilibrium is established. This carbamoyl-migration product has been called iso-bleomycin. Under the same reaction condition, copper-chelated bleomycin does not give iso-bleomycin1), but yields irreversibly another product designated epi-bleomycin. In this communication, the formation, isolation, chemical and biological properties and structure of epi-bleomycin are reported. Preliminary experiments showed that epimerization proceeds slower than isomerization. In order to study the reaction process, liquid chromatography, as shown in Fig. 1, was used for the rapid quantitative determination of the reaction product.