Evaluating indole-related derivatives as precursors in the directed biosynthesis of diazepinomicin analogues.
The effectiveness of precursor-directed biosynthesis to generate diazepinomicin (1) analogues with varied ring-A substitutents was investigated by feeding commercially available, potential ring-A precursors such as fluorinated tryptophans, halogenated anthranilates, and various substituted indoles into growing actinomycete culture DPJ15 (genus Micromonospora). Two new monofluorinated diazepinomicin analogues (2 and 3) were identified and characterized by spectroscopic methods. Both derivatives showed modest antibacterial activity against the Gram-positive coccus Staphylococcus aureus with MIC values in the range 8-32 microg/mL.
Ratnayake
Anokha S
AS
Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA. ratnaya@wyeth.com
Janso
Jeffrey E
JE
Feng
Xidong
X
Schlingmann
Gerhard
G
Goljer
Igor
I
Carter
Guy T
GT
D003984:Dibenzazepines / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008847:Micromonospora / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013211:Staphylococcus aureus / Q000187:drug effects
D003984:Dibenzazepines; D006845:Hydrocarbons, Fluorinated; D007211:Indoles; C492422:diazepinomicin