An expedient synthesis of the amide analog of the potent antifungal lipopeptidolactone FR901469

An expedient synthesis of the lactam analog (2) of the 40-membered lipopeptidolactone antifungal antibiotic, FR901469 (1), is described. The key steps in this synthesis are a novel biotransformation of the natural product to produce the highly versatile linear peptide building block 3, and efficient formation of the 40-membered ring by macrolactamization under high-dilution conditions.