The Total Synthesis of (±)-Fumimycin

• Published in: Chemistry : a European journal Vol. 16; no. 42; pp. 12660 - 12667
• Main Authors: Gross, Patrick J., Bräse, Stefan
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 08-11-2010; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Aldehydes; Amidohydrolases - antagonists & inhibitors; amines; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacteria; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - pharmacology; Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Chains; Chemistry; fumimycin; Imines; inhibitors; Molecular Structure; natural products; Olefins; Oximes; Peptides; Stereoisomerism; Strategy; total synthesis
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201001036

The antibiotic agent fumimycin has been synthesized for the first time. This natural product was found to inhibit the bacterial peptide deformylase and may represent a lead structure to a class of novel antibacterials. Our synthetic strategy towards fumimycin involved the following steps: Dakin oxidation of an aldehyde functionality, conversion of an oxime through radical fragmentation to form an N‐diphenylphosphoryl group, construction of an α‐trisubstituted amine by 1,2‐addition to a ketimine, a Claisen rearrangement with subsequent transition‐metal‐catalyzed olefin isomerization to install a propenyl chain and final amidation.
Peptide deformylase (PDF)‐inhibitor synthesis: A strategy involving amine formation through addition to a ketimine has been successfully employed for the first total synthesis of the antibiotic agent fumimycin (see scheme).