Synthesis of the ABCD segment of the marine biotoxin azaspiracid-1.
Item
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Title
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Synthesis of the ABCD segment of the marine biotoxin azaspiracid-1.
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Identifier
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AAI3325407
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identifier
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3325407
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Creator
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Li, Xiaohua.
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Contributor
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Adviser: David R. Mootoo
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Date
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2008
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Organic
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Abstract
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Azaspiracid is a marine biotoxin natural product that was isolated from the shellfish mytilus edulis in 1997 by Yasamoto's group. It is a novel phytotoxin found to be responsible for an outbreak of diarretic food poisoning associated with consumption of contaminated shellfish in Europe in 1996. Toxicological studies have indicated that the azaspiracids can induce widespread organ damage in mice and their mode of action is distinctly different from previously known shellfish toxins. The remarkable structural complexity and potent bioactivity of the azaspiracids have attracted considerable interest in the synthesis of analogues.;The work reported in this thesis centers on an unusual spiroketalization strategy in which a hydroxyalkene serves as the synthetic equivalent of a cyclic enol ether. This concept was applied to the synthesis of the ABCD trioxadispiroketal subunit of azaspiracid-1. The trioxadispiroketal product, which represents a double anomeric effect was obtained as a single trioxadispiroketal diastereomer. The complexity represented in the ABCD subunit and the convergent nature of this synthesis suggests that the spiroketalization methodology may be suitable for other classes of highly functionalized spiroketals.;A second novel aspect of this synthesis was the use of a cyclopropanylglycal as a precursor for the methylated-C-ring. Towards this end two approaches to complex glycols were explored: an oxocarbenium ion---enol ether cyclization and a ring closing metathesis strategy.;As a summary, total Synthesis of the ABCD segment of the marine biotoxin azaspiracid-1 was achieved in 35 total steps, and 1.5% overall yield with a longest linear sequence of 22 steps.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
