benzofurans and fumimycin

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.

Topics: Anti-Bacterial Agents; Benzaldehydes; Benzofurans; Catalysis; Imines; Magnetic Resonance Spectroscopy; Molecular Structure; Nitriles; Rhodium; Stereoisomerism

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.

Topics: Amidohydrolases; Anti-Bacterial Agents; Benzofurans; Biological Products; Molecular Structure; Stereoisomerism

The first asymmetric total synthesis of fumimycin was accomplished. As a key step, a 1,2-addition of methyl Grignard reagents to ketimines with quinine as additive was employed. The absolute configuration of (+)-fumimycin was determined by CD-spectroscopy combined with time-dependent density functional calculations.

Topics: Benzofurans; Imines; Models, Molecular; Nitriles; Quinine; Spectrum Analysis; Stereoisomerism

Studies towards the synthesis of the bacterial peptide deformylase (PDF) inhibitor fumimycin are reported. The synthetic approach features an organocatalytic access to the alpha,alpha-disubstituted amino acid unit and results in the synthesis of an advanced intermediate which already contains all functionalities of fumimycin.

Topics: Amidohydrolases; Amino Acids; Benzofurans

Fumimycin, an unusual metabolite incorporating an unusual alanine unit linked to a phenyl group at the alpha-carbon with both lactone and amide moieties, was isolated from cultures of Aspergillus fumisynnematus. Its structure was established by spectral analysis. Fumimycin was found to inhibit Staphylococcus aureus peptide deformylase with an IC50 value of 4.1 microM and also showed antibacterial activity against S. aureus.

Topics: Amidohydrolases; Aspergillus; Benzofurans; Molecular Structure; Staphylococcus aureus