Total Synthesis of 13-Desmethyl Spirolide C (SpiroSynth)
Total Synthesis of 13-Desmethyl Spirolide C
Start date: Sep 1, 2012,
End date: Aug 31, 2014
Marine phycotoxins such as spirolides produced by toxic dinoflagellates concentrate in shellfish tissues, and by vectorial transport reach marine animals and humans. In 2005, spirolides have been detected in oysters in the Arcachon bay (France), and sanitary authorities have banned their commercialization, causing heavy losses to shellfish farms around. To date, no toxicological study has been conducted to determine the long-term impact of spirolides on human health due to the low amount available. 13-Desmethyl spirolide C was shown to be the most active of the spirolide family, presenting a potent antagonist effect on nicotinic acetylcholine receptors with only little specificity for a particular receptor subtype. No total synthesis of a spirolide has been described to date. The objective of this research program is to achieve the total synthesis of 13-desmethyl spirolide C using an original strategy by developing a new and convergent method to build up north and south fragments of the target. The north fragment includes a spiroimine skeleton that will be synthesized through a 3-component radical process as a key-step. The south fragment characterized by a bis-spiroketal will be synthesized using a sila-Stetter reaction. The north and south fragments will then be assembled subsequently through a Nozaki-Hiyama-Kishi and a Suzuki coupling. The results obtained during this program will contribute to the development of new methodological methods and provide biologists with sufficient amount of this phycotoxin to carry out toxicological studies. This project is also aimed at training a promising organic chemist from Spain in total synthesis of natural product, a fundamental objective in chemical sciences. This researcher possesses an excellent scientific background with five years experience in carbohydrate chemistry, having led to remarkable achievements. This training period should allow him to enlarge his vision of scientific research and upgrade his personal future.
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