Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Straightforward Access to Hexahydropyrrolo[2,3-b]indole Core by a Regioselective C3-Azo Coupling Reaction of Arenediazonium Compounds with Tryptamines.

ABSTRACT: A base-mediated regioselective electrophilic addition of arenediazonium salts at the C3-position of tryptamines followed by cyclization provides an efficient entry to C3-nitrogenated hexahydropyrrolo[2,3-b]indoles (HPIs) that can subsequently be transformed into 3-arylhexahydropyrrolo[2,3-b]indoles and other HPI derivatives. The reaction is the first example of a 1,2-diamination that utilizes easily accessible arenediazonium salts as nitrogenous electrophiles.

SUBMITTER: Stephens DE

PROVIDER: S-EPMC4233011 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Straightforward Access to Hexahydropyrrolo[2,3-b]indole Core by a Regioselective C3-Azo Coupling Reaction of Arenediazonium Compounds with Tryptamines.

Stephens David E DE Larionov Oleg V OV

European journal of organic chemistry 20140601 17

A base-mediated regioselective electrophilic addition of arenediazonium salts at the C3-position of tryptamines followed by cyclization provides an efficient entry to C3-nitrogenated hexahydropyrrolo[2,3-b]indoles (HPIs) that can subsequently be transformed into 3-arylhexahydropyrrolo[2,3-b]indoles and other HPI derivatives. The reaction is the first example of a 1,2-diamination that utilizes easily accessible arenediazonium salts as nitrogenous electrophiles. ...[more]

PMID: 25408620

Similar Datasets

Hexahydropyrrolo[2,3-b]indole Compounds as Potential Therapeutics for Alzheimer's Disease.

Project description:Alzheimer's disease (AD) is the most common form of dementia among the elderly and has become a leading public health concern worldwide. It represents a huge economic and psychological burden to caregivers and families. The presence of extracellular amyloid beta (Aβ) plaques is one of the hallmarks of this neurodegenerative disorder. Amyloid plaques are comprised of aggregates of Aβ peptides, mainly Aβ42, originated by the cleavage of the amyloid precursor protein (APP). Aβ is a crucial target for the treatment of AD, but to date, no effective treatment for the clearance of Aβ has been found. We have identified four new hexahydropyrroloindoles (HPI) synthetic compounds that are able to inhibit the aggregation of Aβ42 and/or disaggregate the fibril. Docking experiments suggest that the nonpolar component of the interaction of compounds with Aβ42 contributes favorably to the binding free energy of each complex. Molecular dynamics simulations suggested fibril disaggregating activity of compounds 1 via interaction with hydrophobic moieties of the fibril. Consistently, compounds 1 and 2 were able to mitigate Aβ42 fibrils induced death in rat pheochromocytoma cells (PC 12). One of the compounds reduces the formation of Aβ aggregates in vivo and the paralysis associated with Aβ toxicity in Caenorhabditis elegans. Our study thus augments efforts for the identification and characterization of new agents that may help stop or delay the progression of AD.

| S-EPMC8130500 | biostudies-literature

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives.

Project description:A chiral phosphoric acid-catalyzed selenofunctionalization of tryptamine derivatives provides access to 3a-(phenylselenyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole derivatives in high yields and with synthetically useful levels of enantioselectivity (up to 89% ee).

| S-EPMC3740605 | biostudies-literature

C7-derivatization of C3-alkylindoles including tryptophans and tryptamines.

Project description:A versatile strategy for C7-selective boronation of tryptophans, tryptamines, and 3-alkylindoles by way of a single-pot C2/C7-diboronation-C2-protodeboronation sequence is described. The combination of a mild iridium-catalyzed C2/C7-diboronation followed by an in situ palladium-catalyzed C2-protodeboronation allows efficient entry to valuable C7-boroindoles that enable further C7-derivatization. The versatility of the chemistry is highlighted by the gram-scale synthesis of C7-boronated N-Boc-L-tryptophan methyl ester and the rapid synthesis of C7-halo, C7-hydroxy, and C7-aryl tryptophan derivatives.

| S-EPMC4241164 | biostudies-literature

Synthesis of ?-substituted tryptamines by regioselective ring opening of aziridines.

Project description:Functionalized tryptamines are targets of interest for development as small molecule therapeutics. The ring opening of aziridines with indoles is a powerful method for tryptamine synthesis if site selectivity can be controlled. 4-Nitrobenzyl carbamate (PNZ)-protected aziridines undergo regioselective ring opening to produce ?-substituted tryptamines for a series of indoles. The PNZ-protected tryptamines can be further manipulated by PNZ removal under mild conditions.

| S-EPMC4930112 | biostudies-literature

Regioselective synthesis of C3 alkylated and arylated benzothiophenes.

Project description:Benzothiophenes are heterocyclic constituents of important molecules relevant to society, including those with the potential to meet modern medical challenges. The construction of molecules would be vastly more efficient if carbon-hydrogen bonds, found in all organic molecules, can be directly converted into carbon-carbon bonds. In the case of elaborating benzothiophenes, functionalization of carbon-hydrogen bonds at carbon-number 3 (C3) is markedly more demanding than at C2 due to issues of regioselectivity (C3 versus C2), and the requirement of high temperatures, precious metals and the installation of superfluous directing groups. Herein, we demonstrate that synthetically unexplored but readily accessible benzothiophene S-oxides serve as novel precursors for C3-functionalized benzothiophenes. Employing an interrupted Pummerer reaction to capture and then deliver phenol and silane coupling partners, we have discovered a directing group-free method that delivers C3-arylated and -alkylated benzothiophenes with complete regioselectivity, under metal-free and mild conditions.

| S-EPMC5364387 | biostudies-literature

Unbiased C3-Electrophilic Indoles: Triflic Acid Mediated C3-Regioselective Hydroarylation of N-H Indoles.

Project description:The direct dearomative addition of arenes to the C3 position of unprotected indoles is reported under operationally simple conditions, using triflic acid at room temperature. The present regioselective hydroarylation is a straightforward manner to generate an electrophilic indole at the C3 position from unbiased indoles in sharp contrast to previous strategies. This atom-economical method delivers biologically relevant 3-arylindolines and 3,3-spiroindolines in high yields and regioselectivities from both intra- and intermolecular processes. DFT computations suggest the stabilization of cationic or dicationic intermediates with H-bonded (TfOH)n clusters.

| S-EPMC9401073 | biostudies-literature

Copper-catalyzed aerobic oxidative radical alkoxycyclization of tryptamines to access 3-alkoxypyrroloindolines.

Project description:We report a copper-catalyzed alkoxycyclization of tryptamine derivatives with O2 as the sole oxidant, leading to a variety of C3a-alkoxypyrroloindolines in good yields with high diastereoselectivities. This reaction involves an interesting double catalytic cycle in which copper-catalyzed carboamination cyclization is favored to form the C-3 radical pyrrolidinoindoline intermediate, then a copper-catalytic radical alkoxylation reaction proceeds smoothly.

| S-EPMC9033248 | biostudies-literature

Regioselective C5-alkylation and C5-methylcarbamate formation of 2,3-dihydro-4-pyridones and C3-alkylation and C3-methylcarbamate formation of 4-(pyrrolidin-1-yl)furan-2(5H)-one.

Project description:Reactions of N-alkyl-2,3-dihydro-4-pyridones and 4-(pyrrolidin-1-yl)furan-2(5H)-one with aldehydes and triethylsilane in a one-flask procedure provided C5 and C3 alkylated derivatives, respectively. Mannich-type reactions with formaldehyde and carbamates in the presence of lithium perchlorate furnished C5/C3 methylcarbamates.

| S-EPMC4671294 | biostudies-literature

Straightforward Access to Thiocyanates via Dealkylative Cyanation of Sulfoxides.

Project description:Thiocyanates, versatile building blocks in organic synthesis, are shown to be easily accessible via an interrupted Pummerer reaction of sulfoxides. This facile dealkylative functionalization proceeds under mild conditions through electrophilic activation of the sulfoxide partner. The resulting thiocyanate itself can serve as a handle for diversification in a straightforward one-pot procedure.

| S-EPMC8022320 | biostudies-literature

Indole peroxygenase activity of indoleamine 2,3-dioxygenase.

Project description:The heme enzyme indoleamine 2,3-dioxygenase (IDO) was found to catalyze the oxidation of indole by H(2)O(2), with generation of 2- and 3-oxoindole as the major products. This reaction occurred in the absence of O(2) and reducing agents and was not inhibited by superoxide dismutase or hydroxyl radical scavengers, although it was strongly inhibited by L-Trp. The stoichiometry of the reaction indicated a one-to-one correspondence for the consumption of indole and H(2)O(2). The (18)O-labeling experiments indicated that the oxygen incorporated into the monooxygenated products was derived almost exclusively from H(2)(18)O(2), suggesting that electron transfer was coupled to the transfer of oxygen from a ferryl intermediate of IDO. These results demonstrate that IDO oxidizes indole by means of a previously unrecognized peroxygenase activity. We conclude that IDO inserts oxygen into indole in a reaction that is mechanistically analogous to the "peroxide shunt" pathway of cytochrome P450.

| S-EPMC3435167 | biostudies-literature