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Usage

Uses

Used in Pharmaceutical Industry:
(Z)-3-(1H-indol-3-yl)acrylonitrile is used as a building block for the synthesis of various pharmaceutical compounds. Its unique structure allows for the creation of new molecules with potential therapeutic applications, making it a valuable component in drug discovery and development.
Used in Chemical Research:
(Z)-3-(1H-indol-3-yl)acrylonitrile serves as a key intermediate in the synthesis of complex organic molecules. Researchers in the field of organic chemistry utilize (Z)-3-(1H-indol-3-yl)acrylonitrile to explore new reaction pathways and develop innovative synthetic strategies, furthering our understanding of chemical reactivity and bond formation.
Used in Material Science:
(Z)-3-(1H-indol-3-yl)acrylonitrile is used as a component in the development of novel materials with specific properties. Its incorporation into polymers and other materials can lead to new applications in areas such as electronics, sensors, and advanced materials, where its unique structure may impart desirable characteristics.

Upstream product

• 487-89-8 Indole-3-carboxaldehyde 
• 2537-48-6 diethyl 1-cyanomethylphosphonate 
• 372-09-8 cyanoacetic acid 
• 20356-45-0 3-(1H-indol-3-yl)-3-oxo-propionitrile 
• 120-72-9 indole 
• 107-13-1 acrylonitrile 
• 16640-68-9 cyanomethylene triphenylphosphorane 
• 6286-56-2 3-<(2-cyano-2-ethoxycarbonyl)ethenyl>indole 

Downstream Products

• 4414-76-0 1H-indole-3-propiononitrile 

Relevant academic research and scientific papers

Structural Diversification of Hapalindole and Fischerindole Natural Products via Cascade Biocatalysis

Hapalindoles and related compounds (ambiguines, fischerindoles, welwitindolinones) are a diverse class of indole alkaloid natural products. They are typically isolated from the Stigonematales order of cyanobacteria and possess a broad scope of biological activities. Recently the biosynthetic pathway for assembly of these metabolites has been elucidated. In order to generate the core ring system, l-tryptophan is converted into the cis-indole isonitrile subunit before being prenylated with geranyl pyrophosphate at the C-3 position. A class of cyclases (Stig) catalyzes a three-step process, including a Cope rearrangement, 6-exo-trig cyclization, and electrophilic aromatic substitution, to create a polycyclic core. The formation of the initial alkaloid is followed by diverse late-stage tailoring reactions mediated by additional biosynthetic enzymes to give rise to a wide array of structural variations observed in this compound class. Herein, we demonstrate the versatility and utility of the Fam prenyltransferase and Stig cyclases toward the core structural diversification of this family of indole alkaloids. Through the synthesis of cis-indole isonitrile subunit derivatives, and with the aid of protein engineering and computational analysis, we have employed cascade biocatalysis to generate a range of derivatives and gained insights into the basis for substrate flexibility in this system.

γ-Regioselective Functionalization of 3-Alkenylindoles via 1,6-Addition to Extended Alkylideneindolenine Intermediates

Alkylideneindolenines are widely employed key electrophilic intermediates for the α-functionalization of the C-3 side chain of indoles. However, the reactivity of their extended (vinylogous) counterparts has not been carefully explored so far. These intermediates can undergo 1,4- or 1,6-addition with functionalization at α- or γ-position of the side chain, resulting in regioisomeric mixtures of products. This work demonstrates that a complete γ-regioselectivity can be achieved in the reaction of 3-indol-3-yl allylic alcohols with various nucleophiles. This process is catalysed by just 1 mol% zinc(II) triflate at room temperature and entails the 1,6-selective addition of the nucleophile to an extended protonated alkylideneindolenine generated in situ. Indoles, pyrroles, anilines and thiols can be efficiently used as nucleophilic partners for this reaction, delivering the corresponding 3-vinyl substituted, γ-functionalised indole products in moderate to good yields. (Figure presented.).

Palladium-catalyzed intermolecular C3 alkenylation of indoles using oxygen as the oxidant

A general and efficient palladium-catalyzed intermolecular direct C3 alkenylation of indoles using oxygen as the oxidant has been developed. The reaction is of complete regio- and stereoselectivity. All products are E-isomers at the C3-position, and no Z-

L-Proline-catalyzed Knoevenagel condensation: A facile, green synthesis of (E)-ethyl 2-cyano-3-(1H-indol-3-yl)acrylates and (E)-3-(1H-indol-3-yl) acrylonitriles

L-Proline has been utilized as a novel and ecofriendly catalyst in ethanol medium for the Knoevenagel condensation of indole-3-carboxyaldehydes and their N-methyl derivatives 1(a-e) and 4(a-e) with the active methylene compound, ethyl cyanoacetate (2) to afford substituted (E)-ethyl 2-cyano-3-(1H-indol-3-yl) acrylates 3(a-e) and 5(a-e) respectively. These products were reacted with dimethyl sulfate in the presence of PEG-600 as an efficient and green solvent to afford the corresponding N-mthylated derivatives 5(a-e). These Knoevenagel products react with 5% NaOH, yielding (E)-3-(1H-indol-3-yl)acrylonitriles 6(a-e) and 7(a-e). Copyright Taylor & Francis Group, LLC.

Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators

Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan. Herein, we report a structure-activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel derivatives were synthesized, and their TDO inhibitory potency was evaluated. The rationalization of the structure-activity relationships (SARs) revealed essential features to attain high TDO inhibition and notably a dense H-bond network mainly involving His55 and Thr254 residues. Our study led to the identification of a very promising compound (58) displaying good TDO inhibition (Ki = 5.5 μM), high selectivity, and good oral bioavailability. Indeed, 58 was chosen for preclinical evaluation.

Synthetic applications of 3-(cyanoacetyl)indoles and related compounds

Various synthetic applications of 3-(cyanoacetyl)indoles, as well as syntheses of some related indoles, have been investigated. Diethyl 2-(1H-indol-3-yl)-2-oxoethylphosphonate and a methyl derivative thereof have been prepared in one step from indole. Moreover, it was demonstrated that 3-(cyanoacetyl)indoles are useful starting materials for the preparation of for example 3-(1H-indol-3-yl)-3-oxopropanamides, 3-heteroarylindoles or 3-heteroaroylindoles.

1,3-Dinitropropanes: Intermediates to 1,3-diaminopropanes

Reduction of malodinitriles 4 and 10 to the corresponding diamines does not work. - Reduction of dinitro-2-(indol-3-yl)-propanes 13 and 16 and subsequent reaction with K2PtCl4 afford the corresponding dichloroplatinum(II) complexes 14 and 17. Complexes 17 show weak binding affinities to the estrogen receptor and no antitumor activity towards MCF-7 and MDA-MB-2231-cell lines. - Twofold addition of nitromethane to aldehyde 24 is possible.

THE SYNTHESIS OF 3-VINYLINDOLES AND 11H-5-CYANOBENZOCARBAZOLE

The synthesis of 3-vinylindoles through Wadsworth Emmons reactions with 3-formyl and 3-acylindoles is described.Altough 3-formylindoles react directly with phosphonate derivatives, 3-acylindoles need prior activation by N-sulphonation. 11H-5-Cyanobenzocarbazole has been prepared by the oxidative cycloaddition of E-3-(indol-3'-yl) propenonitrile and benzyne.