Multimodule Assembly Strategy toward Total Synthesis of Amphidinolactone B

Amphidinolactone B, isolated from the marine dinolfagellate Amphinium sp., was proposed as a 26-membered macrolide with C6 configuration unassigned. We envisioned a multimodule assembly strategy toward its total synthesis using ring-closing metathesis(RCM) as the ket step . The advanced propargylic alcohol 2 was assembled through lithium acetyide addition with the known aldehyde in the presence of CeCl3. The Au(I)-catalyzed Meyer-Schuster rearrangement of 2 was optimized by suppressing the side reaction of C25-PMB ether. Theresultant enone underwent chemoselective asymmertric dihydroxylation (AD) in the presence of the C12-C13 alkenyl iodide Cross-coupling of the alkyl iodide 3 with 2 was realized via our Aphos-Y-pd(OAc)2-catalyzed B-alkyl Suzuki-Miyaura cross coupling reation Finally, condensation of the two diastereometric acid modules ontthe C25-Oh furnished two seco-intermediates, respectively. The latter underwent smoothly RCM under our carefully modified conditions to produce two C6 diastereosisomer s of Unfortunately none of them matches with the naturally occuring amphinolactone B.