Syntheses of C22–C29 and C20–C29 sections of amphidinol 3

Abstract

Polyol segments corresponding to C22–C29 and C20–C29 sections of amphidinol 3 (AM3) were synthesized as building blocks of artificial analogues of AM3 for structure–activity relationship studies. The C22–C29 section was synthesized from (S)-Roche ester through continuous half-reduction of an ester and a Grignard reaction under flow and batch conditions, followed by iterative ozonolysis and Grignard reactions. The C20–C29 section was derived from the common intermediate of AM3 and the artificial analogue corresponding to the C21–C67 section via olefination and Sharpless asymmetric dihydroxylation.