Modular synthesis of the mycolactone core

ORGN 645

Matthew D. Alexander, mdalexan@ucsd.edu1, James J. La Clair, jlaclair@ucsd.edu1, and Michael D. Burkart, mburkart@ucsd.edu2. (1) Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093, (2) Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358
Mycolactone is a polyketide toxin produced by Mycobacterium ulcerans, which is necessary and sufficient for causing the debilitating skin lesions that characterize the disease known as Buruli Ulcer. While BU is the third most common mycobacterial infection, a viable treatment is still lacking. We have targeted the inhibition of mycolactone biosynthesis for the development of antibiotics against M. ulcerans. Mycolactone was previously synthesized by Kishi through an elegant route that showcased his spectral database approach for the assignment of stereochemistry. Unfortunately, his route does not avail itself to rapid analog production. Therefore, the macrocyclic core of mycolactone has been synthesized using a convergent synthetic route. Our strategy employs general reactions with mild conditions for the parallel construction of three fragments that are ultimately coupled to form the mycolactone core. The approach is designed to be versatile and allow substitution in each of the three fragments for the creation of analogs.

 

Total Synthesis of Complex Molecules
8:00 AM-12:00 PM, Wednesday, 13 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006