ORGN 42 |
First biosynthetic studies of the azinomycins
| Philip A.S. Lowden and Christophe Corre. School of Biological and Chemical Sciences, University of Exeter, Chemistry Building, Stocker Road, Exeter, EX4 4QD, United Kingdom |
The azinomycins are potent antitumour agents isolated from Streptomyces sahachiroi and S. griseofuscus that act by forming inter-strand crosslinks in DNA. Their striking structures have prompted much interest from synthetic chemists and various analogues have been prepared and tested for anti-cancer activity. However, the biosynthetic origin of the azinomycins has remained a mystery until now. We have performed what are to our knowledge the first biosynthetic studies of the azinomycins by feeding 13C-labelled acetate. Our results are consistent with a polyketide origin for the naphthoate fragment, and with the enol fragment arising from threonine. Significant labelling was observed for the aziridine fragment, with a labelling pattern characteristic of the Krebs cycle. These results are consistent with the first five carbons of this fragment arising from alpha-ketoglutarate. Our results will provide a foundation for future biosynthetic engineering of anticancer drugs based on the azinomycins. |
| |
|
Lipids, Biosynthesis, Enzyme Inhibitors, and Mimetics
8:00 AM-11:40 AM, Sunday, September 7, 2003 Sheraton New York -- Royal Ballroom B, Oral
Division of Organic Chemistry
The 226th ACS National Meeting, New York, NY, September 7-11, 2003
|