A concise, total synthesis and antibacterial evaluation of 2-hydroxy-1-(1H-indol-3-yl)-4-methylpentan-3-one.
Treatment of racemic 2-hydroxy-3-(1H-indol-3yl)propionic acid methyl ester (5) with isopropyl magnesium chloride provided the title compound 1 and its isomer, 3-hydroxy-1-(indol-3-yl)-4-methylpentan-2-one (9). Both enantiomers (>96% ee) of each component were obtained via semi-preparative chiral supercritical fluid chromatography (SFC). In contrast to previous reports, these compounds, as well as their acetate derivatives, were not active or very weakly active against 16 bacterial strains, including Escherichia coli, Bacillus subtilis and Staphylococcus aureus.
Nguyen
Son T
ST
Microbiotix, Inc, One Innovation Dr, Worcester, MA 01605, USA. snguyen@microbiotix.com
Butler
Michelle M
MM
Varady
Laszlo
L
Peet
Norton P
NP
Bowlin
Terry L
TL
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007536:Isomerism; D008826:Microbial Sensitivity Tests; D011422:Propionates / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007211:Indoles; D011422:Propionates; C029658:propionic acid