Stereoselective synthesis of the ABCD ring framework of azaspiracids

Abstract

A stereoselective synthesis of the ABCD ring framework of azaspiracid-1 and azaspiracid-3 has been achieved using a tandem bis-spiroketalization protocol in the presence of a mild proton source from 1,4-diketone precursor. A tetrahydrofuran intermediate with the correct stereochemistry for the D ring of azaspiracids-1 and 3 was then taken through a linear sequence of reactions to afford the desired diketone precursor. The D-ring of azaspiracid-1 was then constructed by employing a Sharpless asymmetric dihydroxylation followed by etherification using a homoallyl derivative. The structure of the ABCD ring framework with four contiguous rings was established by extensive NMR analysis.