National Research Council of Canada. Measurement Science and Standards
azaspiracids; total synthesis; structure determination; natural products; toxins
A convergent and stereoselective total synthesis of the previously assigned structure of azaspiracid-3 has been achieved via a late stage NHK coupling to form the C21‒C22 bond with the C20 configuration unambiguously established from L-(+)-tartaric acid. Post-coupling steps involved oxidation to an ynone, modified Stryker reduction of the alkyne, global deprotection, and oxidation of the primary alcohol to the carboxylic acid. The synthetic product matched naturally occurring azaspiracid-3 by mass spectrometry, but differed both chromatographically and spectroscopically.