A strategy toward the total synthesis of durhamycin A, an aureolic acid natural product possessing potent anti-HIV properties, is described. The proposed synthesis utilizes a convergent approach to assemble the highly functionalized tricyclic aglycone, a conserved structural motif among the aureolic acids. The key steps include the [4 + 2] annulation to construct the substituted naphthalene core and the asymmetric allylation to install the polyketide side chain. The proposed synthetic route is highly amenable to analog synthesis, as it would allow late-stage installation of preassembled side chains onto a common central scaffold. Validation of this strategy would enable access to a wide range of aureolic acid analogs, potentially leading to the discovery of novel antibiotic and anti-HIV agents.

Public Health Relevance

The proposed study on the synthesis of durhamycin A will enable access to a wide range of synthetic analogs, which will significantly enhance the discovery efforts on novel antibiotic and anti-HIV agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM090472-02
Application #
8029568
Study Section
Special Emphasis Panel (ZRG1-F04A-B (20))
Program Officer
Fabian, Miles
Project Start
2010-02-16
Project End
2012-01-31
Budget Start
2011-02-16
Budget End
2012-01-31
Support Year
2
Fiscal Year
2011
Total Cost
$46,709
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037