Person:

Smaltz, Daniel Jonathan

Two routes to the 2,6-dideoxysugar methyl trioxacarcinoside A are described. Each was enabled by an apparent α-chelation-controlled addition of an allylmetal reagent to a ketone substrate containing a free α-hydroxyl group and a β-hydroxyl substituent, either free or protected as the corresponding di-tert-butylmethyl silyl ether. Both routes provide practical access to gram-quantities of trioxacarcinose A in a form suitable for glycosidic coupling reactions.

The trioxacarcins are structurally complex, highly oxygenated bacterial isolates that potently inhibit the growth of human cancer cells in culture as a consequence of their ability to alkylate guanosine residues of duplex DNA. This dissertation presents a component-based synthetic route to the trioxacarcin structural class, broadly defined, which resulted in fully synthetic routes to trioxacarcin A (1), DC-45-A1 (10), and a diverse collection of analogs.