Source: Dissertation Abstracts International, Volume: 55-08, Section: B, page: 3307.

Adviser: Samuel J. Danishefsky.

Calicheamicin $\gamma\sb1\sp{\rm I},$ recently isolated from micromonospora echinospora ssp. calichensis, is an extremely potent antitumor antibiotic. This work discusses the total synthesis of the methyl glycoside of the aryl-tetrasaccharide domain. The construction employed glycals as building blocks to minimize protecting group manipulations. Thus, the methyl glycoside was produced in 6% overall yield for 20 steps.

The route was expanded to allow access to an aryl-tetrasaccharide that could be activated as a glycosyl donor in view of the total synthesis of the natural product. Despite encouraging results, the incompatibility between the deprotection sequence and the sensitive functionalities present in the aglycone required a revision of the protecting group strategy. Thus a new amino glycal was synthesized and a TES-protected aryl-tetrasaccharide was elaborated. Subsequent glycosidation of an advanced intermediate of the aglycon with a glycosyl donor derived from this revised aryl-tetrasaccharide followed by final deprotection afforded the fully synthetic drug calicheamicin $\gamma\sb1\sp{\rm I}.$

The successful glycosidation procedure was also used to tentatively elaborate a hybrid between the calicheamicin aryl-tetrasaccharide and the aglycone of the well known antitumor agent daunomycin.