Total synthesis of (+)-A83543A [(+)-lepicidin A]

Article abstract of DOI:10.1021/ja00064a011

The first synthesis of the macrolide insecticide A83543A (lepicidin A) has been completed using a Diels-Alder strategy to construct the carbocyclic framework. Diene synthesis through Pd-catalyzed Stille coupling of a macrocyclic vinylstannane and suitably functionalized vinyl iodide was followed by a diastereoselective Lewis acid-mediated intramolecular Diels-Alder reaction to construct the trans hydrindene subunit. Refunctionalization and intramolecular aldol condensation afforded the differentially protected (+)-lepicidin A aglycon. Successive glycosidations with 2,3,4-tri-O-methyl-D-rhamnose and N-protected L-forosamine followed by deprotection and methylation completed the synthesis of the enantiomer of the natural product.