The development of new and novel synthetic approaches to four different families of antitumor agents is proposed. In this way, systematic structural variation of these classes of compounds with known activity can be performed to develop structure-activity relationships. Catharanthine, one of the alkaloids for a semisynthetic approach to vinblastine and vincristine, will be approached using transition metal chemistry. A novel asymmetric synthesis via a Diels-Alder reaction is also invoked. The second part deals with the antileukemic iridoid allamandin. The strategy develops a new approach to secoalkylation, the development of stereochemistry via the rigid bicyclo(3.3.0)octane, and novel ways to adjust oxidation level of carbon. The third part deals with the aglycone of pillaromycin A which is known to be less toxic than other members of this family such as daunomycin and adriamycin. The approach features a novel way to create a protected phenolic ring, the use of dienes controlled by sulfur substitution, and the development of an unusual new protecting group. Extension to the aglycone of aclacinomycin A is considered. The fourth part deals with verrucarin A which is a member of the family of most potent cytostatic agents known. It is approached using the concept of secoalkylation and modification of oxidation level via organosulfur intermediates. A novel creation of the bicyclo(3.3.1)oxanonane system via a Claisen rearrangement is proposed.
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