Date of Award

1994

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Nikolaus H. Fischer

Abstract

In a biochemical systematic study of the plant family Asteraceae combined with a search for bioactive natural products, the isolation and structural elucidation of secondary metabolites from seven plant species is reported. Investigation of the roots of Solidago canadensis provided six known and one new clerodane diterpenes related to kolavenic acid and five known matricaria ester-type polyacetylenes. The roots and aerial parts of Solidago rugosa afforded the known diterpenes kolavenol, hardwickiic acid, ($-$)-kaur-16-en-19-oic acid, (+)-manool, (+)-3$\beta$-hydroxymanool, manoyl oxide and ent-abietic acid and the new labdane diterpene, (+)-18-tigloyloxymanool, plus four new ent-abietane diterpenes. The isolation of two new and eight known eudesmane-type sesquiterpene cinnamates, and benzyl 2,6-dimethoxybenzoate from the roots of Brintonia discoidea (syn. Solidago discoidea) is reported. The roots of Chrysoma pauciflosculosa (syn. Solidago pauciflosculosa) provided the known polyacetylenes cis,cis- and cis,trans-matricaria esters, a mixture of two isomeric epoxides of matricaria ester, and two known triterpenes, epifriedelinol and friedelin. In addition, the ubiquitous 2,6-dimethoxybenzoquinone and a new benzotropolone were found. The roots of Erigeron philadelphicus afforded, besides the above four polyacetylenes, two isomeric matricaria lactones. The roots of giant ragweed (Ambrosia trifida) afforded thiarubrine B and its related thiophene, as well as a new 1,2-dithia-3,5-cyclohexadiene derivative, 3-(pent-3-yn-1-ynyl)-6-(3,4-epoxy-but-1-ynyl)-1,$2$ -dithiacyclohexa-3,5-diene. The stems of A. trifida gave, besides $\beta$-cubebene and $\alpha$-farnesene, two carotane-type sesquiterpenes, the known lasidiol angelate (1$\alpha$-angeloyloxycarotol) and the new 1$\alpha$-(2$\sp\prime$-methylbutyroyloxy)-carotol, plus 2,6-dimethoxybenzoquinone and hexadecanal. The aerial parts of Liatris ohlingerae afforded five known and two new heliangolide-type sesquiterpene lactones related to liscunditrin and four known triterpenes, taraxasterol, pseudo-taraxasterol and their acetates. The detailed structure elucidation using spectroscopic methods and chemical transformations is described. In order to demonstrate structure-activity relationships, a series of chemical transformations on sesquiterpene lactones were performed. Epoxidation of costunolide yielded 1,10-epoxycostunolide, parthenolide, and the cyclization products santamarin, reynosin, magnolialide and a 1,4-epoxyeudesmenolide. Reduction of santamarin afforded 11,13-dihydrosantamarin and an eudesmen-triol, while reduction of reynosin provided 11,13-dihydroreynosin and two eudesman-triols. The acid-catalyzed transformation of dihydroparthenolide in methanol afforded two guaianolide derivatives. These sesquiterpenes were tested against Mycobacterium tuberculosis and M. avium and the structure-activity relationships among sesquiterpene lactones are discussed. Polyacetylenes from S. canadensis, C. pauciflosculosa and E. philadelphicus also exhibited significant activity against these two strains of mycobacteria.

Pages

279

DOI

10.31390/gradschool_disstheses.5742

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