Synthesis of the C9-C25 Subunit of Spirastrellolide B

The synthesis of the C9-C25 subunit of the marine natural product spirastrellolide B is reported. The key synthetic features included the union of the two key fragments 5 and 6 via a Suzuki-Miyaura coupling reaction and a late-stage, one-pot sequential deprotection/cascade Achmatowicz rearrangement-spiroketalization to install the key spirocyclic intermediate present in the C9-C25 fragment of spirastrellolide B. The synthesis of the C9-C16 fragment 6 was accomplished via a phosphate tether mediated ring-closing metathesis (RCM), a subsequent hydroboration-oxidation protocol, followed by other stereoselective transformations in a facile manner. The spirocyclic intermediate was further functionalized utilizing a Lindlar/NaBH4 reduction protocol to furnish the C9-C25 subunit 3.