Total Synthesis of (6R,10R,13R,14R,16R,17R,19S,20R,21R,24S, 25S,28S,30S,32R,33R,34R,36S,37S,39R)‐Azaspiracid‐3 Reveals Non‐Identity with the Natural Product |
| |
| Authors: | Nathaniel T. Kenton Dr. Daniel Adu‐Ampratwum Dr. Antony A. Okumu Dr. Zhigao Zhang Dr. Yong Chen Dr. Son Nguyen Dr. Jianyan Xu Dr. Yue Ding Dr. Pearse McCarron Dr. Jane Kilcoyne Prof. Dr. Frode Rise Prof. Dr. Alistair L. Wilkins Dr. Christopher O. Miles Prof. Dr. Craig J. Forsyth |
| |
| Affiliation: | 1. Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA;2. Shanghai Hengrui Pharmaceutical Inc., Shanghai, P. R. China;3. Asymchem Life Science, Tianjin, P. R. China;4. Johnson Matthey Pharma Services, Devens, MA, USA;5. Viva Biotech Ltd., Shanghai, China;6. Measurement Science and Standards, National Research Council of Canada, Halifax, Nova Scotia, Canada;7. Marine Institute, Rinville, Oranmore, Co., Galway, Ireland;8. Department of Chemistry, University of Oslo, Oslo, Norway;9. Norwegian Veterinary Institute, Oslo, Norway;10. Chemistry Department, University of Waikato, Hamilton, New Zealand |
| |
| Abstract: | A convergent and stereoselective total synthesis of the previously assigned structure of azaspiracid‐3 has been achieved by a late‐stage Nozaki–Hiyama–Kishi coupling to form the C21?C22 bond with the C20 configuration unambiguously established from l ‐(+)‐tartaric acid. Postcoupling steps involved oxidation to an ynone, modified Stryker reduction of the alkyne, global deprotection, and oxidation of the resulting C1 primary alcohol to the carboxylic acid. The synthetic product matched naturally occurring azaspiracid‐3 by mass spectrometry, but differed both chromatographically and spectroscopically. |
| |
| Keywords: | azaspiracids natural products structure elucidation total synthesis toxins |
|
|
