Total Synthesis of Trioxacarcins DC-45-A1, A, D, C, and C7″-<i>epi</i>-C and Full Structural Assignment of Trioxacarcin C

Trioxacarcins DC-45-A2, DC-45-A1, A, D, C7″-<i>epi</i>-C, and C have been synthesized through stereoselective strategies involving BF₃·Et₂O-catalyzed ketone–epoxide opening and gold-catalyzed glycosylation reactions, and the full structural assignment of trioxacacin C was deciphered via the syntheses of both of its C7″ epimers. The gathered knowledge sets the foundation for the design, synthesis, and biological evalution of analogues of these natural products as potential payloads for antibody–drug conjugates and other delivery systems for targeted and personalized cancer chemotherapy

Streamlined Total Synthesis of Trioxa­carcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxa­carcin Analogues

A streamlined total synthesis of the naturally occurring antitumor agents trioxa­carcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthra­quinones and chloro anthra­quinones from simple ketone precursors and phenyl­selenyl chloride is also described. The reported work, featuring novel chemistry and cascade reactions, has potential applications in cancer therapy, including targeted approaches as in antibody–drug conjugates