21200-24-8

Basic information

• Product Name: (-)-Indolmycin
• Synonyms: (S)-5-[(1R)-1-(1H-Indol-3-yl)ethyl]-2-(methylamino)-4(5H)-oxazolone;[5S,(-)]-5-[(R)-1-(1H-Indol-3-yl)ethyl]-2-methylamino-2-oxazolin-4-one;Pa-155-A
• CAS NO: 21200-24-8
• Molecular Formula: C₁₄H₁₅N₃O₂
• Molecular Weight: 257.2878
• Mol File: 21200-24-8.mol

Chemical Properties

• Melting Point: 209-210°
• Boiling Point: 420.8°Cat760mmHg
• Flash Point: 208.3°C
• Appearance: /
• Density: 1.36g/cm³
• Vapor Pressure: 2.75E-07mmHg at 25°C
• Refractive Index: 1.669
• Solubility: Soluble in ethanol;methanol;DMSO;dimethyl formamide
• PKA: 16.65±0.30(Predicted)
• CAS DataBase Reference: (-)-Indolmycin(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-Indolmycin(21200-24-8)
• EPA Substance Registry System: (-)-Indolmycin(21200-24-8)

Safety Data

• Hazardous Substances Data: 21200-24-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(-)-Indolmycin is used as an antibiotic for its selective action against specific bacteria, making it a valuable tool in the treatment of various infections. Its unique mode of action as a tryptophan anti-metabolite allows it to target and disrupt essential metabolic pathways in bacteria, leading to their inhibition or death.
Used in Antimicrobial Applications:
(-)-Indolmycin is used as an antimicrobial agent, particularly effective against Mycobacteria and Helicobacter pylori. These bacteria are known to cause a range of diseases, including tuberculosis and peptic ulcers, respectively. The compound's activity against these pathogens highlights its potential in combating drug-resistant strains and improving patient outcomes.
Used in Molecular Biology Research:
(-)-Indolmycin is used as a research tool for stimulating transcription in Escherichia coli. This application allows scientists to study the mechanisms of gene expression and regulation, which can lead to a better understanding of bacterial physiology and the development of novel therapeutic strategies.

Biological Activity

indolmycin is an antibiotic.tryptophanyl-trna synthetase (trprs) catalyzes activation of tryptophan through atp and transfer to trnatrp , leading to translation of the genetic code for tryptophan.

in vitro

indolmycin was found to ba a bacteriostatic that showed good activity against methicillin-resistant s. aureus, methicillin-susceptible staphylococcus aureus, and vancomycin-intermediate s. aureus, including strains resistant to mupirocin or fusidic acid. spontaneous indolmycin-resistant mutants was observed at a lower frequency than those selected by mupirocin or fusidic acid and exhibited no cross-resistance with the comparative drugs. high-level resistance of indolmycin at its mic of 128 mg/l that was associated with an h43n mutation in tryptophanyl-trna synthetase, the target enzyme of indolmycin, led to loss of bacterial fitness. however, the locus responsible for low-level indolmycin resistance (indolmycin mics 8-32 mg/l) was not identified [1].

in vivo

animal study found that indolmycin could completely clear h. pylori in experimentally infected mongolian gerbils at a dose of 10 mg/kg. therefore, indolmycin could be regarded as a candidate for the treatment of h. pylori infection [2].

IC 50

30 μm for prokaryotic tryptophanyl-trna synthetase

references

[1] hurdle jg, o'neill aj, chopra i. anti-staphylococcal activity of indolmycin, a potential topical agent for control of staphylococcal infections. j antimicrob chemother. 2004 aug;54(2):549-52. epub 2004 jul 8.[2] vecchione jj, sello jk. a novel tryptophanyl-trna synthetase gene confers high-level resistance to indolmycin. antimicrob agents chemother 2009; 53: 3972-3980.

InChI:InChI=1/C14H15N3O2/c1-8(12-13(18)17-14(15-2)19-12)10-7-16-11-6-4-3-5-9(10)11/h3-8,12,16H,1-2H3,(H,15,17,18)/t8-,12+/m1/s1

Upstream product

• 182194-46-3 2-Dimethylamino-5-[1-(1H-indol-3-yl)-ethyl]-4-oxo-4,5-dihydro-oxazole-5-carboxylic acid benzyl ester 
• 103871-33-6 N-carbobenzoxy-3-(l-chloroethyl)indole 
• 42352-13-6 3-[1-(dimethylamino)ethyl]-1H-indole 
• 487-89-8 Indole-3-carboxaldehyde 
• 74-89-5 methylamine 
• 103871-34-7 5-<1-(1H-indol-3-yl)ethyl>-2-(dimethylamino)-4(5H)-oxazolone 
• 26622-60-6 (2S,3R)-2-hydroxy-3-(1H-indol-3-yl)butanoic acid 
• 150131-72-9 ethyl (2S,3R)-2-hydroxy-3-(1H-indol-3-yl)butanoate 
• 20906-48-3 (5S)-2-amino-5-[(1R)-1-(1H-indol-3-yl)ethyl]-2-oxazolin-4-one 
• 74639-51-3 3-[(2R,3S)-3,4-Dimethyl-5,7-dioxo-2-phenyl-[1,4]oxazepan-(6Z)-ylidenemethyl]-indole-1-carboxylic acid benzyl ester 
• 74639-51-3 3-[(2R,3S)-3,4-Dimethyl-5,7-dioxo-2-phenyl-[1,4]oxazepan-(6E)-ylidenemethyl]-indole-1-carboxylic acid benzyl ester 
• 74639-52-4 (S)-3-(1H-indol-3-yl)-butyric acid methyl ester 
• 214541-53-4 (S)-3-(3-indolyl)butanoic acid 
• 74639-56-8 1-Methyl-3-[(2S,3R)-3-[1-(tetrahydro-pyran-2-yl)-1H-indol-3-yl]-2-(tetrahydro-pyran-2-yloxy)-butyryl]-thiourea 

Downstream Products

• 201536-79-0 (5S)-2-(N-benzyloxycarbonyl-N-methyl)amino-5[(1R)-1-(indol-3-yl)ethyl]-2-oxazolin-4-one 
• 201536-84-7 (5S)-2-[N-(2-benzyloxybenzoyl)-N-methyl]amino-5-[(1R)-1-(indol-3-yl)ethyl]-2-oxazolin-4-one 
• 201536-81-4 (5S)-5-[(1R)-1-(indol-3-yl)ethyl]-2-[N-(N-(4-methoxyphenyl)carbamoyl)-N-methyl]amino-2-oxazolin-4-one 
• 201536-87-0 (5S)-2-[N-(N-benzyloxycarbonyl-L-alanyl)-N-methyl]amino-5-[(1R)-1-(indol-3-yl)ethyl]-2-oxazolin-4-one 

Relevant articles and documents

An engineered biosynthetic-synthetic platform for production of halogenated indolmycin antibiotics

Indolmycin is an antibiotic fromStreptomyces griseusATCC 12648 with activity againstHelicobacter pylori,Plasmodium falciparum, and methicillin-resistantStaphylococcus aureus. Here we describe the use of the indolmycin biosynthetic genes inE. colito make indolmycenic acid, a chiral intermediate in indolmycin biosynthesis, which can then be converted to indolmycin through a three-step synthesis. To expand indolmycin structural diversity, we introduce a promiscuous tryptophanyl-tRNA synthetase gene (trpS) into ourE. coliproduction system and feed halogenated indoles to generate the corresponding indolmycenic acids, ultimately allowing us to access indolmycin derivatives through synthesis. Bioactivity testing against methicillin-resistantStaphylococcus aureusshowed modest antibiotic activity for 5-, 6-, and 7-fluoro-indolmycin.

A concise synthesis of (-)-indolmycin and (-)-5-methoxyindolmycin

Concise syntheses of (-)-indolmycin 1 and (-)-5-methoxyindolmycin 3 were developed based on a palladium-catalyzed reaction of (2S,3R)-2-acetoxy-3-methyl-5-trimethylsilyl-4-pentynoate 6 with an o-iodoaniline derivative 10 or 11, followed by reaction with g

Process for producing indolmycins

A process for producing indolmycin or a salt thereof which comprises reacting a compound of the formula: or a salt thereof with methylamine or a salt thereof, can be produced in an optically active form in a high yield and high quality, and is advantageous from the industrial point of view.

Development of a stereoselective practical synthetic route to indolmycin, a candidate anti-H. pylori agent

A stereoselective practical synthetic route to indolmycin is described. The route is composed of the regioselective coupling of indolyl magnesium halide with a trans-epoxy ester, diastereoselective oxazolone ring formation with guanidine and amine exchang

Structure-activity dependency of new bacterial tryptophanyl tRNA synthetase inhibitors

Analogues of the aminoacyl tRNA synthetase inhibitor, indolmycin, have been synthesised in which the side chain methyl group is replaced by a wide range of substituents. Their antibacterial and enzyme inhibitory potency is related to steric properties and

Total synthesis of (±) indolmycin

A practical and short synthesis of a novel antibiotic, (±) indolmycin, has been accomplished. The overall process requires only 4 chemical steps by starting from gramine derivative 3 and oxazolinone 2.

New Total Synthesis of (+/-)-Indolmycin

A convergent total synthesis of the antibiotic (+/-)-indolmycin (1) is presented.N-Carbobenzoxy-3-(1-chloroethyl)indole (12) is prepared in three steps from indole-3-carboxaldehyde (9).Alkylation of the lithium anion of 2-(dimethylamino)-4(5H)-oxazolone (4) with chloride (12) provides a mixture of the (+/-)-2-dimethylamino derivative of indolmycin (13) and its diastereomer (14) in a ratio of 2.2:1.Amine exchange is effected by treatment of 13 with methylamine, affording (+/-)-1 in five steps from commercially available 9.Efforts to extend this technology toward an asymmetric synthesis of (-)-1 are described.

ASYMMETRIC TOTAL SYNTHESIS OF INDOLMYCIN

An asymmetric total synthesis of indolmycin was achieved via a key intermediate, α-indolmycenic acid ester.The ester was obtained by oxygenation of methyl (S)-3-(3-indolyl)butanoate which was prepared by asymmetric synthesis utilizing (2R,3S)-3,4-dimethyl