January 2023 - Page 9 of 26 - Indole Building Blocks

Oderinde, Martins S. et al. published their research in Journal of Organic Chemistry in 2021 | CAS: 167631-84-7

Methyl 5-fluoro-1H-indole-2-carboxylate (cas: 167631-84-7) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Product Details of 167631-84-7

Photocatalytic Dearomative Intermolecular [2 + 2] Cycloaddition of Heterocycles for Building Molecular Complexity was written by Oderinde, Martins S.;Ramirez, Antonio;Dhar, T. G. Murali;Cornelius, Lyndon A. M.;Jorge, Christine;Aulakh, Darpandeep;Sandhu, Bhupinder;Pawluczyk, Joseph;Sarjeant, Amy A.;Meanwell, Nicholas A.;Mathur, Arvind;Kempson, James. And the article was included in Journal of Organic Chemistry in 2021.Product Details of 167631-84-7 This article mentions the following:

Indole and indoline rings are important pharmacophoric scaffolds found in marketed drugs, agrochems., and biol. active mols. The [2 + 2] cycloaddition reaction is a versatile strategy for constructing architecturally interesting, sp³-rich cyclobutane-fused scaffolds with potential applications in drug discovery programs. A general platform for visible-light mediated intermol. [2 + 2] cycloaddition of indoles with alkenes has been realized. A substrate-based screening approach led to the discovery of tert-butyloxycarbonyl (Boc)-protected indole-2-carboxyesters as suitable motifs for the intermol. [2 + 2] cycloaddition reaction. Significantly, the reaction proceeds in good yield with a wide variety of both activated and unactivated alkenes, including those containing free amines and alcs., and the transformation exhibits excellent regio- and diastereoselectivity. Moreover, the scope of the indole substrate is very broad, extending to previously unexplored azaindole heterocycles that collectively afford fused cyclobutane containing scaffolds that offer unique properties with functional handles and vectors suitable for further derivatization. DFT computational studies provide insights into the mechanism of this [2 + 2] cycloaddition, which is initiated by a triplet-triplet energy transfer process. The photocatalytic reaction was successfully performed on a 100 g scale to provide the dihydroindole analog. In the experiment, the researchers used many compounds, for example, Methyl 5-fluoro-1H-indole-2-carboxylate (cas: 167631-84-7Product Details of 167631-84-7).

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Jiang, Lin-Ling et al. published their research in Tetrahedron Letters in 2007 | CAS: 146368-07-2

1-Ethyl-2,3,3-trimethyl-3H-indol-1-ium-5-sulfonate (cas: 146368-07-2) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Quality Control of 1-Ethyl-2,3,3-trimethyl-3H-indol-1-ium-5-sulfonate

An efficient approach to the synthesis of water-soluble cyanine dyes using poly(ethylene glycol) as a soluble support was written by Jiang, Lin-Ling;Dou, Li-Fang;Li, Bao-Lin. And the article was included in Tetrahedron Letters in 2007.Quality Control of 1-Ethyl-2,3,3-trimethyl-3H-indol-1-ium-5-sulfonate This article mentions the following:

An efficient synthesis approach to unsym. water-soluble amphoteric cyanine dyes has been established. Loading and activation of a sulfoindolenium inner salt on polyethylene glycol (PEG) as a first step have been achieved via a simple strategy. The cyanine dyes are released by the attack of a heterocyclic carbon nucleophile and the cleavage of the PEG-bound hemicyanine. The efficient approach delivers cyanine dyes in high purity without the nontrivial chromatog. separation often encountered in a solution process. In the experiment, the researchers used many compounds, for example, 1-Ethyl-2,3,3-trimethyl-3H-indol-1-ium-5-sulfonate (cas: 146368-07-2Quality Control of 1-Ethyl-2,3,3-trimethyl-3H-indol-1-ium-5-sulfonate).

Hou, Shaohua et al. published their research in European Journal of Medicinal Chemistry in 2021 | CAS: 16732-64-2

4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2) belongs to indole derivatives. The indole subunit is an almost ubiquitous component of biologically active natural products, and its study has been the focus of research for decades. It is used in perfumery and in making tryptophan, an essential amino acid, and indoleacetic acid (heteroauxin), a hormone that promotes the development of roots in plant cuttings.Synthetic Route of C9H6BrNO2

Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis was written by Hou, Shaohua;Yang, Xiping;Tong, Yu;Yang, Yuejing;Chen, Quanwei;Wan, Boheng;Wei, Ran;Wang, Yuchen;Zhang, Yanmin;Kong, Bo;Huang, Jianhang;Chen, Yadong;Lu, Tao;Hu, Qinghua;Du, Ding. And the article was included in European Journal of Medicinal Chemistry in 2021.Synthetic Route of C9H6BrNO2 This article mentions the following:

Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) family, is implicated in many human diseases. Here, we describe the structural optimization of a hit compound and conduct further structure-activity relationship (SAR) studies that result in the development of the indole-2-carboxamide I. I displays potent anti-ASK1 kinase activity and stronger inhibitory effect on ASK1 in AP1-HEK293 cells than previously described ASK1 inhibitor GS-4997. Besides improved in vitro activity, I also exhibits an appropriate in vivo PK profile. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), I shows significant anti-UC efficacy and markedly attenuates DSS-induced body weight loss, colonic shortening, elevation in disease activity index (DAI) and inflammatory cell infiltration in colon tissues. Mechanistically, I represses the phosphorylation of ASK1-p38/JNK signaling pathways and suppresses the overexpression of inflammatory cytokines. Together, these findings suggest that ASK1 inhibitors can potentially be used as a therapeutic strategy for UC. In the experiment, the researchers used many compounds, for example, 4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2Synthetic Route of C9H6BrNO2).

Kahnberg, Pia et al. published their research in Journal of Medicinal Chemistry in 2006 | CAS: 16732-64-2

4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). Related Products of 16732-64-2

Design, Synthesis, Potency, and Cytoselectivity of Anticancer Agents Derived by Parallel Synthesis from α-Aminosuberic Acid was written by Kahnberg, Pia;Lucke, Andrew J.;Glenn, Matthew P.;Boyle, Glen M.;Tyndall, Joel D. A.;Parsons, Peter G.;Fairlie, David P.. And the article was included in Journal of Medicinal Chemistry in 2006.Related Products of 16732-64-2 This article mentions the following:

Chemotherapy in the last century was characterized by cytotoxic drugs that did not discriminate between cancerous and normal cell types and were consequently accompanied by toxic side effects that were often dose limiting. The ability of differentiating agents to selectively kill cancer cells or transform them to a nonproliferating or normal phenotype could lead to cell- and tissue-specific drugs without the side effects of current cancer chemotherapeutics. This may be possible for a new generation of histone deacetylase inhibitors derived from amino acids. Structure-activity relationships are now reported for 43 compounds derived from 2-aminosuberic acid that kill a range of cancer cells, 26 being potent cytotoxins against MM96L melanoma cells (IC₅₀ 20 nM-1 μM), while 17 were between 5- and 60-fold more selective in killing MM96L melanoma cells vs. normal (neonatal foreskin fibroblasts, NFF) cells. This represents a 10- to 100-fold increase in potency and up to a 10-fold higher selectivity over previously reported compounds derived from cysteine (J. Med. Chem. 2004, 47, 2984). Selectivity is also an underestimate, because the normal cells, NFF, are rarely all killed by the drugs that also induce selective blockade of the cell cycle for normal but not cancer cells. Selected compounds were tested against a panel of human cancer cell lines (melanomas, prostate, breast, ovarian, cervical, lung, and colon) and found to be both selective and potent cytotoxins (IC₅₀ 20 nM-1 μM). Compounds in this class typically inhibit human histone deacetylases, as evidenced by hyperacetylation of histones in both normal and cancer cells, induce expression of p21, and differentiate surviving cancer cells to a nonproliferating phenotype. These compounds may be valuable leads for the development of new chemotherapeutic agents. In the experiment, the researchers used many compounds, for example, 4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2Related Products of 16732-64-2).

Padwa, Albert et al. published their research in Journal of Organic Chemistry in 1994 | CAS: 6639-06-1

3-(1H-Indol-1-yl)propanoic acid (cas: 6639-06-1) belongs to indole derivatives. Indole, also called Benzopyrrole, a heterocyclic organic compound occurring in some flower oils, such as jasmine and orange blossom, in coal tar, and in fecal matter. In addition to indole, the strain-release chemistry worked for numerous substrates including amines, alcohols, thiols, carboxylic acids, imidazoles, and pyrazoles.Name: 3-(1H-Indol-1-yl)propanoic acid

Intramolecular Cycloaddition of Isomunchnone Dipoles to Heteroaromatic π-Systems was written by Padwa, Albert;Hertzog, Donald L.;Nadler, William R.. And the article was included in Journal of Organic Chemistry in 1994.Name: 3-(1H-Indol-1-yl)propanoic acid This article mentions the following:

A series of furanyl-, thienyl-, and indolo-substituted diazo imides were prepared by treating the appropriate amides with diketene to give the N-acetoacylated imides. Exposure of the imides to standard diazo transfer conditions afforded the desired diazo imides. Treatment of these diazo imides bearing tethered heterocyclic rings with rhodium(II) acetate affords transient isomuenchnone dipoles. The mesoionic dipoles are formed by cyclization of the rhodium carbenoid onto the neighboring amide carbonyl oxygen atom. The scope and limitations of the intramol. 1,3-dipolar cycloaddition of the isomuenchnones across a tethered furan and thiophene ring were studied. The facility of the internal cycloaddition is influenced by the length and nature of the tether connecting the dipole and dipolarophile functionalities. The reaction is critically dependent on conformational factors in the transition state. In addition, the first examples of intramol. cycloaddition of isomuenchnones to indole dipolarophiles are reported. Cycloadditions of this type generate highly functionalized polyheterocyclic systems with complete relative stereocontrol at the newly formed stereocenters. In the experiment, the researchers used many compounds, for example, 3-(1H-Indol-1-yl)propanoic acid (cas: 6639-06-1Name: 3-(1H-Indol-1-yl)propanoic acid).

Matviitsuk, Anastassia et al. published their research in Angewandte Chemie, International Edition in 2019 | CAS: 14204-27-4

2-(Phenylthio)isoindoline-1,3-dione (cas: 14204-27-4) belongs to indole derivatives. Indole, also called Benzopyrrole, a heterocyclic organic compound occurring in some flower oils, such as jasmine and orange blossom, in coal tar, and in fecal matter. Moreover, it is known that it controls biofilm formation. However, the role of indole in the cell has not been fully elucidated.Category: indole-building-block

Enantio- and Diastereoselective, Lewis Base Catalyzed, Cascade Sulfenoacetalization of Alkenyl Aldehydes was written by Matviitsuk, Anastassia;Denmark, Scott E.. And the article was included in Angewandte Chemie, International Edition in 2019.Category: indole-building-block This article mentions the following:

In the presence of a nonracemic selenophosphoramide Lewis base, 5-hexenal and ortho-alkenylbenzaldehydes such as 2-allyl-4-methylbenzaldehyde underwent diastereoselective and enantioselective sulfenoacetalization reactions with N-(2,6-diisopropylphenylthio)phthalimide in hexafluoroisopropanol to yield nonracemic sulfenyl acetals such as I and isochroman acetals such as II. In the experiment, the researchers used many compounds, for example, 2-(Phenylthio)isoindoline-1,3-dione (cas: 14204-27-4Category: indole-building-block).

Li, Zhenhua et al. published their research in Heterocycles in 2022 | CAS: 112656-95-8

7-Nitroindoline-2,3-dione (cas: 112656-95-8) belongs to indole derivatives. In addition to tryptophan, indigo, and indoleacetic acid, numerous compounds obtainable from plant or animal sources contain the indole molecular structure. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Synthetic Route of C8H4N2O4

Efficient synthesis of novel spiro[indoline-3,5′-pyrano-[2,3-d]pyrimidin]-2-one derivatives and antitumor activity evaluation was written by Li, Zhenhua;Huang, Guoqing;Rong, Dayou;Cao, Yingyan;Hu, Ronghui. And the article was included in Heterocycles in 2022.Synthetic Route of C8H4N2O4 This article mentions the following:

An efficient method for synthesis of the spiro[indoline-3,5′-pyrano[2,3-d]pyrimidin]-2-one derivatives I [R¹ = H, 7-Me, 5-Cl, etc.; R² = H, Me; R³ = CN, C(O)Me, CO₂Et; R⁴ = Me, Ph] from 2′-amino-2-oxospiro[indoline-3,4;-pyran]-3′-carbonitriles using bis(trichloromethyl) carbonate (BTC) and triphenylphosphine oxide (TPPO) was developed. A series of target compounds I with broad substrate scope were synthesized in moderate to good yields. Some of the compounds I were evaluated for antitumor activities against four cancer cell lines A549, HepG-2, MCF-7 and HeLa using 5-FU and cisplatin as reference and showed good antitumor activity when compared with the standard drugs. In the experiment, the researchers used many compounds, for example, 7-Nitroindoline-2,3-dione (cas: 112656-95-8Synthetic Route of C8H4N2O4).

Zou, Zirong et al. published their research in Journal of Organic Chemistry in 2021 | CAS: 5388-42-1

2-Phenylisoindolin-1-one (cas: 5388-42-1) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. In addition to indole, the strain-release chemistry worked for numerous substrates including amines, alcohols, thiols, carboxylic acids, imidazoles, and pyrazoles.Reference of 5388-42-1

Metal-Free Cascade Formation of Intermolecular C-N Bonds Accessing Substituted Isoindolinones under Cathodic Reduction was written by Zou, Zirong;Cai, Genuo;Chen, Weihao;Zou, Canlin;Li, Yamei;Wu, Hongting;Chen, Lu;Hu, Jinhui;Li, Yibiao;Huang, Yubing. And the article was included in Journal of Organic Chemistry in 2021.Reference of 5388-42-1 This article mentions the following:

An electrochem. protocol for the construction of substituted isoindolinones I (R¹ = H, 5-Me, 6-Cl, etc.; R² = Ph, c-hexyl, 2-furyl, etc.) via reduction/amidation of 2-carboxybenzaldehydes and amines has been realized. Under metal-free and external-reductant-free electrolytic conditions, the reaction achieves the cascade formation of intermol. C-N bonds and provides a series of isoindolinones in moderate to good yields. The deuterium-labeling experiment proves that the hydrogen in the methylene of the product is mainly provided by H2O in the system. In the experiment, the researchers used many compounds, for example, 2-Phenylisoindolin-1-one (cas: 5388-42-1Reference of 5388-42-1).

Khalafy, Jabbar et al. published their research in Australian Journal of Chemistry in 1998 | CAS: 5388-42-1

2-Phenylisoindolin-1-one (cas: 5388-42-1) belongs to indole derivatives. Indole, also called Benzopyrrole, a heterocyclic organic compound occurring in some flower oils, such as jasmine and orange blossom, in coal tar, and in fecal matter. Moreover, it is known that it controls biofilm formation. However, the role of indole in the cell has not been fully elucidated.HPLC of Formula: 5388-42-1

Flash vacuum pyrolysis of some N-benzylbenzotriazoles and N-benzylbenzisoxazolones was written by Khalafy, Jabbar;Prager, Rolf H.. And the article was included in Australian Journal of Chemistry in 1998.HPLC of Formula: 5388-42-1 This article mentions the following:

The flash vacuum pyrolysis products of 2-(benzotriazol-1-ylmethyl)benzonitrile, Me 2-(benzotriazol-1-ylmethyl)benzoate, and the corresponding benzisoxazolones have been characterized. The benzotriazoles lose nitrogen to give diradicals, which undergo intramol. hydrogen-atom transfer or cyclization, while the benzisoxazolones rearrange initially to the corresponding benzaldehyde N-(2-carboxyphenyl)imines, which undergo subsequent intramol. addition reactions. In the experiment, the researchers used many compounds, for example, 2-Phenylisoindolin-1-one (cas: 5388-42-1HPLC of Formula: 5388-42-1).

Barltrop, J. A. et al. published their research in Journal of the Chemical Society in 1954 | CAS: 16732-64-2

4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Category: indole-building-block

Synthesis of lysergic acid. I. Derivatives of indole was written by Barltrop, J. A.;Taylor, D. A. H.. And the article was included in Journal of the Chemical Society in 1954.Category: indole-building-block This article mentions the following:

As a model for the synthesis of lysergic acid, 2-methyl-3(2-oxocyclohexylidenemethyl)indole (I), prepared by condensing 2-methylindole (II) with formylcyclohexanone (III), was reduced to 2-methyl-3-(2-oxocyclohexylmethyl)indole (IV) and cyclized in small yield to a tetracyclic system (V), 4,6,6a,7,8,9-or 4,6,7,8,9,10-hexahydro-5-methyldibenz[cd,f] isoindole. An alternative, involving the cyclization of 4-bromo-3(2-oxocyclohexylmethyl)indole by an intramol. Grignard reaction, failed since the essential intermediate, 4-bromoindole (VI), could not be prepared II (9.5 g.) and 20 g. III in EtOH refluxed 2 h. gave 10 g. I, yellow prisms, m. 126° (from EtOH); dinitrophenylhydrazone, orange needles, m. 234°. I (0.67 g.) in EtOH hydrogenated at room temperature and pressure over Pd-C 1 h. gave IV, a colorless oil; picrate, m. 135° (from C₆H₆); semicarbazone, plates, m. 199-200° (decomposition). Indole (2 g.) and 4 g. III refluxed 2 h. in EtOH also gave 3-(2-oxocyclohexylidenemethyl)indole, needles, m. 232°. 2-Phenylindole and III in EtOH gave a blue substance, m. 200°, which is apparently of complex structure. IV (1 g.) was stirred 2 min. at 130° in 4 g. P₂O₅ and 3 cc. sirupy H₃PO₄, the insoluble residue dissolved in MeOH, the solution brought to pH 6, 2 g. Girard’s reagent “P” added, and the solution refluxed 20 min. The residue yielded the picrate of V, red needles, m. 144°. When 9.3 g. IV in 50 cc. PhMe was refluxed 1 h. with P₂O₅ no ketone fraction could be isolated. 2,6-Br(O₂N)C₆H₃Me (VII) (1 kg. crude), recrystallized, yielded 400 g. pure VII, m. 42°, and 500 g. 4,2-Br(O₂N)C₆H₃Me (VIII), m. 47°. VII (216 g.) and 143 g. (CO₂Et)₂, refluxed 45 min. with NaOEt in EtOH give 119 g. 2,6-Br(O₂N)C₆H₃CH₂COCO₂H (IX), m. 117° (from C₆H₆); semicarbazone, m. 216°. From the steam distillate was recovered 115 g. VII. Similarly VIII gave 40% 4,2-Br(O₂N)C₆H₃CH₂COCO₂H (X), needles, m. 144°, and 51% unchanged VIII. IX (28 g.) reduced in a refluxing solution of 150 g. FeSO₄.7H₂O and 60 cc. NH₄OH in 600 cc. H₂O 5 min. gave 18 g. 4-bromo-2-indolecarboxylic acid (XI), m. 266° (from EtOH). IX (28 g.) and 45 cc. 10% NaOH in 100 cc. H₂O treated during 1 h. with 53 g. Na₂S₂O₄, and the solution acidified with HCl and heated 2 h. gives 22 g. XI. Similarly X gave the 6-Br isomer of XI, needles, m. 223° (from aqueous EtOH). VII (21.6 g.) suspended in 50 cc. EtOH, hydrogenated with Raney Ni at room temperature and 3 atm. pressure, gave 17 g. 6,2-Br(H₂N)C₆H₃Me (XII), b₁₆ 130°. XII (9.3 g.) heated overnight in 20 cc. anhydrous HCO₂H gave 10 g. N-formyl derivative, (XIII), leaflets, m. 116°. 4,2-Br(HCONH)C₆H₃Me, needles, m. 137°, was similarly prepared from VIII. XIII (16 g.) added to 2.9 g. K in 100 cc. tert-BuOH, the alc. distilled, and the residue heated 0.5 h. to 270° did not form any VI. 6,2-Br(AcNH)C₆H₃Me (34 g.) warmed under N with 14 g. NaNH₂ until evolution of NH₃ ceased, then heated 15 min. at 240°, did not afford 4-bromo-2-methylindole. Me 2-bromocinnamate (11.4 g.) in concentrated H₂SO₄ treated during 0.5 h. at 0° with 3.5 g. HNO₃ (d. 1.48) in 10 cc. H₂SO₄ gave 13.7 g. crude product which, triturated with MeOH, yielded 9.5 g. Me 2-bromo-5-nitrocinnamate (XIV), yellow needles, m. 169° (from MeOH). XIV (6 g.) suspended in 50% H₂SO₄ and refluxed a few min. with a saturated solution of 7 g. KMnO₄ gave 2.4 g. 2,5-Br(O₂N)C₆H₃Me, needles, m. 178° (from aqueous EtOH). In the experiment, the researchers used many compounds, for example, 4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2Category: indole-building-block).