ARS | Publication request: Improved Synthesis of a Dimethylfuran-Containing Macrolide

Submitted to: American Chemical Society Abstracts
Publication Type: Abstract Only
Publication Acceptance Date: August 20, 2009
Publication Date: N/A

Technical Abstract: The synthetic pathway to the furan-containing macrolide pheromone of Galerucella beetles was shortened from 13 steps in the original synthesis to 10 steps, and the overall yield was increased greater than six fold. A concise Reformatsky-based sequence of reactions was utilized to construct the key precursor, 2,3-dimethyl-2-butenolide. Reduction of the butenolide with diisobutylaluminum hydride afforded 3,4-dimethylfuran. A one-pot sequence of lithiation, alkylation by a THP-containing iodide, a second lithiation, and finally formylation gave the required tetrasubstituted furan intermediate, 3,4-dimethyl-5-[5-(tetrahydrofuran-2-yloxy)pentyl]-2-furaldehyde. After construction of the saturated 3-carbon acyl side chain and removal of protective groups, the lactone ring was closed using the Mitsunobu method. The pheromone can be used to monitor populations of G. calmariensis and G. pusilla (Coleoptera: Chrysomelidae), which have been introduced into North America as biological control agents for the invasive wetland weed, purple loosestrife (Lythrum salicaria).