The syntheses of trichiliasterone A and B isolated from Trichilia hirta and the preparation of derivatives of the antimalarial agent gedunin.

Abstract

This thesis describes the first total synthesis of 2-hydroxyandrosta-1,4-diene-3,16-dione, trichiliasterone A, 1, the transformation of 1 into 2-methoxyandrosta-1,4-diene-3,16-dione 1a, and the partial synthesis of trichiliasterone B, 3$\beta$-hydroxypregna-2,16-dione 2. Steroids 1 and 2 were isolated from the wood of the Costa Rican tree, Trichilia hirta, and both elicited insect growth inhibition in the European corn borer, Ostrinia nubilalis and the variegated cutworm, Peridroma saucia. Steroid 1a was isolated from Trichilia americana. In addition to the syntheses of 1 and 2, derivatives of gedunin 74, a limonoid currently under development as an antimalarial agent, were prepared. The 1-benzylmercaptogedunin derivative 78 was prepared in connection with the postulated molecular mode of action of gedunin 74. The derivative, 7-hydroxygedunin 75 was prepared to test its stability under acidic conditions. Finally, 7-methoxygedunin 77 was prepared and tested for antimalarial activity against a chloroquine resistant (W2) and chloroquine sensitive (D6) strain of Plasmodium falciparum.