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Synthesis of the Phormidolide A Macrocycle Supports the Proposed Configurational Reassignment
Garrett Muir1, Ian Paterson2, Nelson Y S Lam2,3
1Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada.
Abstract:
We describe the successful synthesis of the phormidolide A macrocycle as a crucial step toward its total synthesis and configurational assignment. Exhaustive exploration of macrocyclization strategies revealed the detrimental effects of a bulky protecting group on the C17 hydroxyl function, leading to the successful use of a C17 p-methoxybenzyloxymethyl (PMBM) ether in the macrolactonization reaction. Further elaboration of the macrocycle with a truncated C18-C23 side chain afforded an advanced C1-C23 fragment of phormidolide A. Detailed comparison of spectroscopic data with those of phormidolide A supports the proposed configurational reassignment.
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