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The first part of this thesis describes the structure elucidation of nine natural products, including three previously unreported compounds, by modern nuclear magnetic resonance techniques. Two new abietanoid diterpenes were isolated from two different species of Salvia: 8-hydroxy-12-oxo-abieta-9(11),13-dien-20-oic acid 8,12-lactone (1) from S. wiedemannii and (5)6-enolic-7-a-diketone-abieta-8(9),11(12),13(14)-triene (2) from S. trijuga. In addition to those new diterpenes, another diterpene isolated from S. hypargeia by Turkish workers and misassigned as xanthoperol by these workers now is corrected as taxodione (3), a known antitumor diterpenoid quinone methide, which had been originally isolated from Taxodium distichum by Kupchan. The third new compound is a triterpenoid saponin isolated from the Chinese traditional medicine Nothopanax davidii, identified as 3-O- (usd\alphausd-L-arabinopyranosyl-(1-2)-usd\alphausd-L-arabinopyranosyl) -olean-12-ene-28,29-dioic acid-28-O-usd\alphausd-L-usd\rm rhamnopyranosylusd-(1-4)-usd\betausd-D-usd\rm glucopyranosylusd-(1-6)-usd\betausd-D-glucopyranoside (4). Four other known triterpene saponins were also isolated from the plants of Araliaceae family, and two dimensional NMR studies resulted in the complete proton and carbon assignments for these compounds (5-8). The final natural product, compound 9, isolated from Aconitum carmichaeli, was shown to have the same structure as hokbusine A, and extensive two dimensional NMR studies led to the correction of previously misassigned carbon chemical shifts for hokbusine A. Molecular modeling calculations and chemical conversions were also utilized in the stereochemical studies of the new compounds. The second part of this thesis focuses on the synthesis and identification of neurotoxic serotonin derivatives. Serotonin is a neurotransmitter existing naturally in animal brains, and its abnormal oxidation products are believed to be related to mental diseases. Oxidation of serotonin by various oxidizing agents has suggested a possible oxidation pathway for the transformation in vivo. One important oxidation product, tryptamine-4,5-dione was obtained in high yield (>90%) by the oxidation of serotonin carbamate with benzeneseleninc acid, which provided a practical approach to prepare the tryptamine-4,5-dione for both structure analysis and pharmacological tests. Tryptamine-4,5-dione carbamate showed high neurotoxicity toward chicken embryo forebrain neurons. The examination of tryptamine-4,5-dione reactivity toward model sulfur and nitrogen nucleophiles indicated the high potential of this o-quinone to react in Michael fashion at the C-7 position. Such reactivity could mimic the reaction with the active sites of the serotonin receptor and G-proteins in the brain, resulting in neurotoxicity. ftn*All degree requirements completed in 1992, but degree will be granted in 1993.
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