Date of Award

1991

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Nikolaus H. Fischer

Abstract

Oxidative chemical transformations of sesquiterpene lactones have been carried out to determine the effect these changes have on the biological activities of these derivatives. Vacuum liquid chromatography was used extensively to isolate the sesquiterpene lactones used for these synthetic transformations. Costunolide and dehydrocostuslactone were isolated from Costus Resinoid (Saussurea lappa) and dihydroparthenolide was isolated from Ambrosia artemisiifolia. The enolate oxidations of sesquiterpene lactones with oxygen and (camphorylsulfonyl)oxaziridine have been investigate. Enolate oxidations of sesquiterpene lactones with oxygen generate low yields of both 11$\alpha$- and 11$\beta$-hydroxylactones. The yields of enolate oxidations with (camphorylsulfonyl)oxaziridine are much improved (over oxygen) and the reaction is stereospecific. This methodology was used to prepare a series of 11-hydroxysesquiterpene lactones of various skeletal types. Two naturally occurring sesquiterpene lactones (11$\beta$,15-dihydroxysaussurea lactone and 15-hydroxydihydrocostunolide) were synthesized from costunolide. These transformations involved the use of enolate oxidations developed previously, allylic oxidations with selenium dioxide, and Cope rearrangements of 1,5-dienes. A hydroperoxy-sesquiterpene lactone (peroxydihydroparthenolide) was synthesized via an ene reaction between an alkene and singlet oxygen. The first biomimetic conversion of a germacrolide to a heliangolide was achieved using tert-butyl hydroperoxide and selenium dioxide supported on silica gel. Other attempted allylic oxidations of a 1,10-epoxygermacrolide with selenium dioxide resulted in isolation of only transannular cyclization products or oxidatively modified cyclization products.

Pages

254

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