A pharmacophore-directed retrosynthesis strategy applied to rameswaralide provided simplified analogs bearing the common 5,5,6 and 5,5,7 skeleton present in several cembranoid and norcembranoids from <i>Sinularia </i>soft corals. Given resemblance to many cembranoid and norcembranoid natural products, these core skeletons may be utilized for future access to other natural products including yonarolide and ineleganolide. Key steps include a kinetic resolution Diels–Alder lactonization organocascade delivering the common 5,5,6 core and a subsequent ring expansion affording a 5,5,7 core serviceable for annulation of the remaining carbons necessary for the total synthesis of rameswaralide. Furthermore, initial structure–activity relationships of intermediates <i>en route </i>to rameswaralide have revealed interesting differential and selective cytotoxicity.

Pharmacophore-directed retrosynthesis applied to rameswaralide: Synthesis and bioactivity of sinularia natural product tricyclic cores

ACS Spring Meeting 2021

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