10590-73-5

Usage

Uses

Used in Pharmaceutical Industry:
3-Methyl-1H-indole-2-carboxylic acid is used as an intermediate in the synthesis of various pharmaceuticals for its potential anti-inflammatory, anti-cancer, and anti-microbial properties. Its ability to modulate biological pathways and target specific diseases makes it a valuable compound in the development of new medications.
Used in Agrochemical Industry:
In the agrochemical sector, 3-methylisatin is utilized as a precursor in the production of agrochemicals, contributing to the development of effective and environmentally friendly solutions for pest control and crop protection.
Used in Dye and Pigment Industry:
3-Methyl-1H-indole-2-carboxylic acid is employed as an intermediate in the synthesis of dyes and pigments, offering a wide range of color options and properties for various applications, including textiles, plastics, and printing inks.
Used in Organic Compounds Synthesis:
This versatile chemical serves as a key component in the synthesis of other organic compounds, expanding its utility across different industries and contributing to the development of innovative products with diverse applications.

InChI:InChI=1/C10H9NO2/c1-6-7-4-2-3-5-8(7)11-9(6)10(12)13/h2-5,11H,1H3,(H,12,13)

Upstream product

• 83-34-1 3-Methylindole 
• 79-37-8 oxalyl dichloride 
• 26304-51-8 ethyl 3-methyl-indole-2-carboxylate 
• 65613-25-4 2,2,2-trifluoro-1-(3-methyl-indol-2-yl)-ethanone 
• 64-17-5 ethanol 
• 70263-59-1 2-(phenylhydrazono)butanoic acid 
• 15719-64-9 methylammonium carbonate 
• 600-18-0 2-Oxobutyric acid 
• 615-43-0 2-iodophenylamine 
• 59-88-1 phenylhydrazine hydrochloride 
• 120-72-9 indole 
• 594-19-4 tert.-butyl lithium 
• 73-22-3 L-Tryptophan 
• 1859-70-7 N-(2-acetylphenyl)-4-methylbenzenesulfonamide 

Downstream Products

• 7511-17-3 3-methyl-indole-2-carboxylic acid dimethylamide 
• 26304-51-8 ethyl 3-methyl-indole-2-carboxylate 
• 120608-03-9 3-methyl-1H-indole-2-carbonyl chloride 
• 120608-11-9 2-[(3-Methyl-1H-indole-2-carbonyl)-amino]-benzoic acid ethyl ester 
• 82594-99-8 3-phenylthieno<3,4-b>indole 
• 82595-00-4 3-phenylseleno<3,4-b>indole 
• 82594-94-3 1,2-dibenzoyl-3-methylindole 
• 82594-96-5 3-phenyl-4-benzoylthieno<3,4-b>indole 
• 82594-97-6 3-phenyl-4-benzoylseleno<3,4-b>indole 
• 82594-95-4 1,2-dibenzoyl-3-bromomethylindole 
• 83-34-1 3-Methylindole 
• 1352805-53-8 1-[1-(3-fluorophenyl)-3-methyl-1H-indol-2-yl]ethanamine 
• 1352805-52-7 1-[1-(3-fluorophenyl)-3-methyl-1H-indol-2-yl]ethanone 
• 1352805-51-6 1-(3-fluorophenyl)-N-methoxy-N,3-dimethyl-1H-indole-2-carboxamide 

Relevant academic research and scientific papers

Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase

The radical S-adenosyl-L-methionine tryptophan lyase NosL converts L-tryptophan into 3-methylindolic acid, which is a precursor in the synthesis of the thiopeptide antibiotic nosiheptide. Using electron paramagnetic resonance spectroscopy and multiple L-tryptophan isotopologues, we trapped and characterized radical intermediates that indicate a carboxyl fragment migration mechanism for NosL. This is in contrast to a proposed fragmentation-recombination mechanism that implied Cα-Cβ bond cleavage of L-tryptophan. Although NosL resembles related tyrosine lyases, subtle substrate motions in its active site are responsible for a fine-tuned radical chemistry, which selects the Cα-C bond for disruption. This mechanism highlights evolutionary adaptation to structural constraints in proteins as a route to alternative enzyme function.

Mechanistic study of the radical SAM-dependent amine dehydrogenation reactions

The radical SAM enzyme NosL catalyzes the conversion of l-Trp to 3-methyl-2-indolic acid, and this reaction is initiated by the 5′-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction from the l-Trp amino group. We demonstrate here that when d-Trp was used in the NosL reaction, hydrogen abstraction occurs promiscuously at both the amino group and Cα of d-Trp. These results inspired us to establish the detailed mechanism of l-Trp amine dehydrogenation catalyzed by a NosL mutant, and to engineer a novel radical SAM-dependent l-Tyr amine dehydrogenase from the thiamine biosynthesis enzyme ThiH.

Synthesis of the core structure of phalarine

The core skeleton of phalarine was rapidly synthesised through novel palladium-catalysed dearomative spirocyclisation and a palladium-catalysed Wacker-carbonylative cyclisation cascade. The two key steps allowed for the efficient construction of a tricyclic propeller skeleton bearing contiguous tetrasubstituted carbon centres, within 3 steps from a topologically planar precursor.

Radical-mediated enzymatic carbon chain fragmentation-recombination

The radical S-adenosylmethionine (S-AdoMet) superfamily contains thousands of proteins that catalyze highly diverse conversions, most of which are poorly understood, owing to a lack of information regarding chemical products and radical-dependent transformations. We here report that NosL, involved in forming the indole side ring of the thiopeptide nosiheptide (NOS), is a radical S-AdoMet 3-methyl-2-indolic acid (MIA) synthase. NosL catalyzed an unprecedented carbon chain reconstitution of L-tryptophan to give MIA, showing removal of the C' ±-N unit and shift of the carboxylate to the indole ring. Dissection of the enzymatic process upon the identification of products and a putative glycyl intermediate uncovered a radical-mediated, unusual fragmentation- recombination reaction. This finding unveiled a key step in radical S-AdoMet enzyme-catalyzed structural rearrangements during complex biotransformations. Additionally, NosL tolerated fluorinated L-tryptophan as the substrate, allowing for production of a regiospecifically halogenated thiopeptide that has not been found among the more than 80 members of the naturally occurring thiopeptide family.

Tryptophan Lyase (NosL): A Cornucopia of 5′-Deoxyadenosyl Radical Mediated Transformations

Tryptophan lyase (NosL) is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the formation of 3-methyl-2-indolic acid from l-tryptophan. In this paper, we demonstrate that the 5′-deoxyadenosyl radical is considerably more versatile in its chem

Mechanistic Studies on Tryptophan Lyase (NosL): Identification of Cyanide as a Reaction Product

Tryptophan lyase (NosL) catalyzes the formation of 3-methylindole-2-carboxylic acid and 3-methylindole from l-tryptophan. In this paper, we provide evidence supporting a formate radical intermediate and demonstrate that cyanide is a byproduct of the NosL-catalyzed reaction with l-tryptophan. These experiments require a major revision of the NosL mechanism and uncover an unanticipated connection between NosL and HydG, the radical SAM enzyme that forms cyanide and carbon monoxide from tyrosine during the biosynthesis of the metallo-cluster of the [Fe-Fe] hydrogenase.

Crystal structure of tryptophan lyase (NosL): Evidence for radical formation at the amino group of tryptophan

Streptomyces actuosus tryptophan lyase (NosL) is a radical SAM enzyme which catalyzes the synthesis of 3-methyl-2-indolic acid, a precursor in the synthesis of the promising antibiotic nosiheptide. The reaction involves cleavage of the tryptophan Cα-Cβ bond and recombination of the amino-acid-derived-COOH fragment at the indole ring. Reported herein is the 1.8 ? resolution crystal structure of NosL complexed with its substrate. Unexpectedly, only one of the tryptophan amino hydrogen atoms is optimally placed for H abstraction by the SAM-derived 5'-deoxyadenosyl radical. This orientation, in turn, rules out the previously proposed delocalized indole radical as the species which undergoes Cα-Cβ bond cleavage. Instead, stereochemical considerations indicate that the reactive intermediate is a ·NH tryptophanyl radical. A structure-based amino acid sequence comparison of NosL with the tyrosine lyases ThiH and HydG strongly suggests that an equivalent ·NH radical operates in the latter enzymes.

Mechanistic Insights into the Radical S-adenosyl- l -methionine Enzyme NosL from a Substrate Analogue and the Shunt Products

The radical S-adenosyl-l-methionine (SAM) enzyme NosL catalyzes the transformation of l-tryptophan into 3-methyl-2-indolic acid (MIA), which is a key intermediate in the biosynthesis of a clinically interesting antibiotic nosiheptide. NosL catalysis was i

Substrate-Tuned Catalysis of the Radical S-Adenosyl- L -Methionine Enzyme NosL Involved in Nosiheptide Biosynthesis

NosL is a radical S-adenosyl-L-methionine (SAM) enzyme that converts L-Trp to 3-methyl-2-indolic acid, a key intermediate in the biosynthesis of a thiopeptide antibiotic nosiheptide. In this work we investigated NosL catalysis by using a series of Trp analogues as the molecular probes. Using a benzofuran substrate 2-amino-3-(benzofuran-3-yl)propanoic acid (ABPA), we clearly demonstrated that the 5′-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction in NosL catalysis is not from the indole nitrogen but likely from the amino group of L-Trp. Unexpectedly, the major product of ABPA is a decarboxylated compound, indicating that NosL was transformed to a novel decarboxylase by an unnatural substrate. Furthermore, we showed that, for the first time to our knowledge, the dAdo radical-mediated hydrogen abstraction can occur from an alcohol hydroxy group. Our study demonstrates the intriguing promiscuity of NosL catalysis and highlights the potential of engineering radical SAM enzymes for novel activities.

The Catalytic Mechanism of the Class C Radical S-Adenosylmethionine Methyltransferase NosN

S-Adenosylmethionine (SAM) is one of the most common co-substrates in enzyme-catalyzed methylation reactions. Most SAM-dependent reactions proceed through an SN2 mechanism, whereas a subset of them involves radical intermediates for methylating non-nucleophilic substrates. Herein, we report the characterization and mechanistic investigation of NosN, a class C radical SAM methyltransferase involved in the biosynthesis of the thiopeptide antibiotic nosiheptide. We show that, in contrast to all known SAM-dependent methyltransferases, NosN does not produce S-adenosylhomocysteine (SAH) as a co-product. Instead, NosN converts SAM into 5′-methylthioadenosine as a direct methyl donor, employing a radical-based mechanism for methylation and releasing 5′-thioadenosine as a co-product. A series of biochemical and computational studies allowed us to propose a comprehensive mechanism for NosN catalysis, which represents a new paradigm for enzyme-catalyzed methylation reactions.