Stereochemical Definition of the Natural Product (6R,10R,13R, 14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R,33R,34R,36S,37S,39R)-Azaspiracid-3 by Total Synthesis and Comparative Analyses

Nathaniel T Kenton; Daniel Adu-Ampratwum; Antony A Okumu; Pearse McCarron; Jane Kilcoyne; Frode Rise; Alistair L Wilkins; Christopher O Miles; Craig J Forsyth

doi:10.1002/anie.201711008

Stereochemical Definition of the Natural Product (6R,10R,13R, 14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R,33R,34R,36S,37S,39R)-Azaspiracid-3 by Total Synthesis and Comparative Analyses

Angew Chem Int Ed Engl. 2018 Jan 15;57(3):810-813. doi: 10.1002/anie.201711008. Epub 2017 Dec 15.

Authors

Affiliations

¹ Department of Chemistry and Biochemistry, The Ohio State University, 151 W. Woodruff Ave, Columbus, OH, 43210, USA.
² Measurement Science and Standards, National Research Council of Canada, 1411 Oxford St., Halifax, Nova Scotia, B3H 3Z1, Canada.
³ Marine Institute, Rinville, Oranmore, Co., Galway, Ireland.
⁴ Department of Chemistry, University of Oslo, 0315, Oslo, Norway.
⁵ Norwegian Veterinary Institute, P.O. Box 750 Sentrum, 0106, Oslo, Norway.
⁶ Chemistry Department, University of Waikato, Private Bag 3105, 3240, Hamilton, New Zealand.

PMID: 29193497
DOI: 10.1002/anie.201711008

Abstract

The previously accepted structure of the marine toxin azaspiracid-3 is revised based upon an original convergent and stereoselective total synthesis of the natural product. The development of a structural revision hypothesis, its testing, and corroboration are reported. Synthetic (6R,10R,13R,14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R, 33R,34R,36S,37S,39R)-azaspiracid-3 chromatographically and spectroscopically matched naturally occurring azaspiracid-3, whereas the previously assigned 20R epimer did not.

Keywords: azaspiracids; natural products; structure elucidation; total synthesis; toxins.

Publication types

Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Biological Products / chemical synthesis*
Biological Products / chemistry*
Carbon-13 Magnetic Resonance Spectroscopy
Chromatography, Liquid
Furans / chemical synthesis*
Furans / chemistry*
Mass Spectrometry
Molecular Structure
Oxidation-Reduction
Proton Magnetic Resonance Spectroscopy
Pyrans / chemical synthesis*
Pyrans / chemistry*
Stereoisomerism

Substances

Biological Products
Furans
Pyrans
azaspiracid-3