In this study, we synthesized the C8–C20 and C21–C30 segments of the diarrhetic shellfish toxin pectenotoxin 2. The C8–C20 segment was assembled from a phosphonate corresponding to the C8–C15 segment (prepared from l-malic acid in 19 steps) and an aldehyde corresponding to the C16–C20 segment (synthesized from 3-methyl-3-butenol in nine steps) by a twelve-step process including the Horner–Wadsworth–Emmons reaction, regio- and stereoselective reduction of the resulting enone, diastereoselective epoxidation, and 5-exo epoxide cleavage forming the C-ring. The C21–C30 segment was constructed in 13 steps from (S)-glycidol via a route involving E-ring formation by 5-exo epoxide cleavage and stereoselective methylation at C27 by the Evans method.

The common left-half [C31–C33(OC1–C7)–C40] part of pectenotoxins has been synthesized convergently from the C31–C35, C36–C40, and C1–C7 parts. The C31–C35 part, prepared via a new route shorter than our previous route, was coupled with the C36–C40 part through reductive lithiation and addition reactions to give an adduct stereoselectively, which was converted to a cyclic acetal corresponding to the C31–C40 part. The left-half was synthesized by a three-step process including esterification of the C31–C40 part with the C1–C7 part.