Not one, not two, but three: Total syntheses of amphidinolides B, G, and H, which exhibit strong, nanogram-scale cytotoxicity against various tumor cell lines, have been executed. The synthetic strategy relied on implementation of a diene construction protocol and a diastereoselective aldol process. The 26- and 27-membered macrocyclic lactone rings were efficiently constructed by using ring-closing metathesis (RCM).

A new approach to the synthesis of the C7-26 fragment of amphidinolides G and H was developed. In the sequence, the C7-18 portion of this fragment was synthesized using an acetylide coupling protocol, while an Evans alkylation and Sharpless asymmetric dihydroxylation were employed as key steps in construction of the C19-26 subfragment. Finally, both of these units were joined by utilizing an aldol coupling reaction to produce the target C7-26 fragment in good yield.

Nicht eins, nicht zwei, sondern drei: Die drei Titelverbindungen, die in Nanogramm‐Mengen gegen Tumorzelllinien wirksam sind, wurden durch Totalsynthesen hergestellt. Neben einem Protokoll zur Dien‐Konstruktion kamen ein diastereoselektiver Aldolprozess und Ringschlussmetathesen (RCM) zum Aufbau der 26‐ und 27‐gliedrigen Makrolactonringe zur Anwendung.