Synthesis of Methoxyfumimycin with 1,2-Addition to Ketimines

Abstract

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.

Synthesis and Characterization of Novel Aromatic Substituted γ- and δ-Ketoxime Esters

“…γ-and δketo esters as starting materials were synthesized by Friedel-Crafts acylation (41,42). General procedure : preparation of oxime esters (43,44) As a general procedure, the keto ester (1.0 eq) 1a-j was dissolved in ethanol.…”

Design and synthesis of 4′‐((5‐benzylidene‐2,4‐dioxothiazolidin‐3‐yl)methyl)biphenyl‐2‐carbonitrile analogs as bacterial peptide deformylase inhibitors

“…In the past few years, different classes of PDF inhibitor like peptidic inhibitors, pseudopeptidic inhibitors, and non‐peptidic inhibitors as antibacterial agents have been reported . The non‐peptidic PDF inhibitors, which are assumed to be less prone to degradation, are not much explored . The non‐peptidic inhibitors like biaryl acid analogs were developed by Merck Research Laboratories and evaluated as PDF inhibitor against Escherichia coli PDF enzyme.…”

“…[12] The non-peptidic PDF inhibitors, which are assumed to be less prone to degradation, are not much explored. [13][14][15][16][17][18] The non-peptidic inhibitors like biaryl acid analogs were developed by Merck Research Laboratories and evaluated as PDF inhibitor against Escherichia coli PDF enzyme. A representative structure for these biaryl acid analogs is shown in Figure 1.…”

A Concise Synthesis of (±)-Methoxyfumimycin Ethyl Ester

“…4-Allyloxy-3-methoxybenzaldehyde (3): 8 A suspension of vanillin 3 (2.87 g, 18.86 mmol) and K 2 CO 3 (3.64 g, 26.40 mmol) in acetone (28 mL), was treated with allylbromide (2.10 mL, 24.51 mmol). The mixture was heated to reflux for 6 h. After filtration, the filtrate was concentrated under reduced pressure.…”

“…Allyloxy-3-methoxyphenol (4):8 Boric acid (5.72 g, 92.30 mmol) was suspended in a mixture of THF (50 mL), H 2 O 2 (30% in H 2 O, 6 mL) and H 2 SO 4 (2.66 mL, 98%). After stirring for 30 min, 3 (3.55 g， 18.47 mmol) was added as solution in THF (20 mL) over 15 min.…”