Synthesis of methoxyfumimycin with 1,2-addition to ketimines.
The synthesis of (+/-)-methoxyfumimycin, a potential new bacterial peptide deformylase (PDF) inhibitor, is reported. To generate the stereogenic fully substituted carbon, the key step is a 1,2-addition of a methyl Grignard reagent to a ketimine. The overall synthetic strategy involves a Dakin oxidation of a vanillin derivative, Friedel-Crafts acylation, Claisen rearrangement, lactonization, and rhodium-catalyzed olefin isomerization.
Gross
Patrick J
PJ
Institute of Organic Chemistry, Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, D-76131 Karlsruhe, Germany.
Hartmann
Caroline E
CE
Nieger
Martin
M
Bräse
Stefan
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001547:Benzaldehydes / Q000737:chemistry*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D007097:Imines / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D001547:Benzaldehydes; D001572:Benzofurans; D007097:Imines; D009570:Nitriles; C522224:fumimycin; C542835:ketimine; C100058:vanillin; D012238:Rhodium