Toward the total synthesis of Griseusin antibiotics

ORGN 96

Thomas L. Mindt, Thomas.Mindt@pharma.ethz.ch, Department of Chemistry, Brown University, Providence, RI 02912 and Kathlyn A Parker, Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794.
The Griseusins are aromatic, polyketide derived antibiotics produced by the actinomycete strain Streptomyces griseus. They are active against gram positive bacteria including MRSA (methillium resistant Staphylococcus aureus). We wish to present an efficient and modular approach for the synthesis of Griseusin antibiotics. Thus, a short reaction sequence for the assembly of the three main building blocks (haloquinone, glycal and vinylstannane) was developed. The obtained advanced intermediates contain the complete carbon skeleton of the natural product appropriately functionalised for completion of the total synthesis. Key steps of the presented work including an application of Parker's “umpolung strategy” for the regioselective synthesis of quinone-glycal conjugates and a dienol-phenol type rearrangement of glycal quinol intermediates will be discussed.