Amphidinolide K : a methodology application

The symbiont dinoflagellate Amphidinium is an incredible biological manufacturing unit. According to our knowledge, 35 interesting molecules, termed Amphidinolides, have been isolated from Amphidinium sp. In 1989, Kobayashi discovered at least 10 Amphidinolides (A-J) that show cytotoxic activities against murine leukemia P388, L1210 cells and human epidermoid carcinoma KB cells. Four years later, Kobayashi isolated a new molecule, Amphidinolide K. Three total syntheses of Amphidinolide K have been reported by Williams, Lee and Vilarrasa. One of the big challenges is the exo-methylene THF pattern. We became interested in the synthesis of this molecule after discovery of a fortuitous ring contraction by the Marko group that allows ready access to exo-methylene THF moieties. Combined with the ene-IMSC sequence, this methodology represents a powerful tool to synthesize the THF ring of Amphidinolide K. Based on this idea, our approach towards this target involved a 3-fragment disconnection. The coupling of these units, based on in-situ hydroboration for Miyaura-Suzuki cross coupling and Julia-Kociensky olefination were investigated.
(SC - Sciences) -- UCL, 2021