1. Antimycobacterial Activities of Dehydrocostus Lactone and Its Oxidation Products
- Author
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Cantrell, C. L., Nunez, I. S., Castaneda-Acosta, J., Foroozesh, M., Fronczek, F. R., Fischer, N. H., and Franzblau, S. G.
- Abstract
In an attempt to study the structural dependence of antimycobacterial activity of the guaianolide dehydrocostus lactone and its derivatives, m-chloroperoxybenzoic acid oxidations of dehydrocostus lactone (
1a ) were performed. Three new monoepoxides, one previously synthesized diepoxide, and two new diepoxides were obtained. Two of the monoepoxides are C-10 epimers (3a, 3b ), while the 4(15)-monoepoxide (2 ) has the 4α-O-configuration. The known diepoxide (4a ) contains a C-10 α-epoxide and a β-epoxide at C-4. The diepoxides4b and4c , each with a C-4 α-epoxy group, differ in the configuration of the epoxide ring at C-10. Allylic oxidation of dehydrocostus lactone (1a ) with selenium dioxide/tert-butyl hydroperoxide afforded the known 3-epizaluzanin C (1b ). The relative configurations of compounds1b − 4c were established by 1D and 2D NMR techniques (1H, 13C, COSY, NOESY, HMQC, and HMBC) as well as comparison with literature data. The molecular structures of lactones1b ,4a , and4c were determined by single-crystal X-ray diffraction. In radiorespirometric bioassays against Mycobacterium tuberculosis and Mycobacterium avium, dehydrocostus lactone (1a ) exhibited minimum inhibitory concentrations of 2 and 16 μg/mL, respectively. In contrast, its monoepoxides (2 ,3a , and3b ) and diepoxides (4a −c ), as well as its hydrogenated derivatives and other analogues (1b ,1c ,5 , and6 ), showed significantly lower activities against M. tuberculosis.- Published
- 1998