Reaction Of Tryptamine Research Articles

Synthesis of C(3) SCF3-Substituted Pyrrolidinoindoline by PIII/PV Redox Catalysis Using CF3SO2Cl as Electrophilic CF3S Reagent.

This work reports a method for the catalytic synthesis of C(3) SCF3-substituted pyrrolidinindoline using a small-ring organophosphorus-based catalyst and a hydrosilane reductant, with trifluoromethanesulfonyl chloride as the electrophilic SCF3 reagent. This method can drive the conversion of tryptamine to the C(3) SCF3-substituted pyrrolidine indoline. The readily available, inexpensive trifluoromethanesulfonyl chloride could be activated as an electrophilic SCF3 source by PIII/PV redox catalysis and could efficiently participate in the reaction of tryptamines, thus providing various substituted C(3) SCF3-substituted pyrrolidinoindoline in moderate to excellent yields. This presented strategy features a broad substrate scope, and the structure has value for in-depth research.

Synthesis, Spectral Identification, Thermal and Antioxidant Studies for Ni (II), Pd (II), Pt (IV) and Au (III) Complexes With New Azo Ligand Derivatives from Tryptamine

In this study, a new Azo ligand 5-((2-(1H-indol-2-yl)ethyl)diazinyl)-2-aminophenol is synthesized from a reaction of Tryptamine with 2-aminophenol. The ligand and their metal ion complexes Ni(II), Pd(II) , Pt(IV) and Au(III) have been synthesized and characterized by various analytical techniques, including elemental microanalysis, metal content, chloride-containing, measurement of electrical conductivity, magnetic susceptibility, 1H and 13C-NMR, FT-IR, UV-Vis, mass spectra (MS), and thermal analysis (TGA and DSC) curves. The DCS curve was used to calculate the thermodynamic parameters ΔH, ΔS, and ΔG. The characterization results promote the metal complexes of azo ligand structures. The results indicate that the ligand behaves as a trident N, N, and O donor ligand for each and every produced complex, and the molar conductivity of all complexes indicates that none of the complexes were electrolytes. The antioxidant activity of the synthesized compounds was evaluated and determined against the DPPH radical (1.1-diphenyl-2-picrylhydrazyl) and compared to that of a standard natural antioxidant, gallic acid. The results show that the metal complexes are more effective at scavenging free radicals.

Uncovering the Mechanism of Azepino-Indole Skeleton Formation via Pictet-Spengler Reaction by Strictosidine Synthase: A Quantum Chemical Investigation.

Strictosidine synthase (STR) catalyzes the Pictet-Spengler (PS) reaction of tryptamine and secologanin to produce strictosidine. Recent studies demonstrated that the enzyme can also catalyze the reaction of non-natural substrates to form new alkaloid skeletons. For example, the PS condensation of 1H-indole-4-ethanamine with secologanin could be promoted by the STR from Rauvolfia serpentina (RsSTR) to generate a rare class of skeletons with a seven-membered ring, namely azepino-[3,4,5-cd]-indoles, which are precursors for the synthesis of new compounds displaying antimalarial activity. In the present study, the detailed reaction mechanism of RsSTR-catalyzed formation of the rare seven-membered azepino-indole skeleton through the PS reaction was revealed at the atomic level by quantum chemical calculations. The structures of the transition states and intermediates involved in the reaction pathway were optimized, and the energetics of the complete reaction were analyzed. Based on our calculation results, the most likely pathway of the enzyme-catalyzed reaction was determined, and the rate-determining step of the reaction was clarified. The mechanistic details obtained in the present study are important in understanding the promiscuous activity of RsSTR in the formation of the rare azepino-indole skeleton molecule and are also helpful in designing STR enzymes for the synthesis of other new alkaloid skeleton molecules.

Polymer‐Supported Phosphoric‐Acid Catalysed Enantioselective Pictet‐Spengler Cyclisation for the Synthesis of Quaternary Tryptolines in Batch/Continuous Flow

AbstractThe enantioselective Pictet‐Spenlger reaction of tryptamines and diketo compounds catalyzed by a polymer‐supported phosphoric acid (TRIP) has been accomplished for the first time in continuous flow. Using this approach, a diverse library of quaternary tryptolines has been synthesized in 36–95% yield with 39–99% enantiomeric excess. The scalability of the reaction has been demonstrated in continuous flow, with a residence time of only 24 minutes. The robust immobilized catalyst has been recycled and reused multiple times in batch and flow. The synthesis of the chiral precursors of Tadalafil, the Iboga‐type alkaloid (+)‐Tabertinggine and antimalarial spiroindolinones has been achieved in batch and continuous‐flow.magnified image

ЦИТОТОКСИЧНОСТЬ ПИРАНОПИРИДОНОВ С ТРИПТАМИНОВЫМ ФРАГМЕНТОМ

New derivatives of pyrano[3,2-c]pyridones III 5, 10, 15, 18 were synthesised by threecomponent reaction of pyridonotryptamines I, aromatic aldehydes II and malononitril. Pyridonotryptamines I were synthesised by reaction of tryptamines (these compounds were obtained by Grandberg reaction of arylhydrazines with γ-halogencarbonyl compounds) with 4-hydroxy- 6-methyl-2H-pyran- 2-on. The aromatic aldehydes II 1, 5, 6, 9 are commercially available compounds. Boiling a mixture of compounds I, II and malononitril (molar ratio 1:1.1:1.1) in ethyl alcohol in the presence of triethylamine gives the target compounds III 5, 10, 15, 18. The product yields 44–75%. The structure of pyrano[3,2-c]pyridones with tryptamine fragment III (four compounds) was proved by 1H NMR and confirmed by elemental analysis. Compounds III 1–4, 6–9, 11–14, 16 and 17 were synthesised earlier by a similar procedure. The cytotoxicity of the synthesised compounds III 1–18 was determined in vitro using the MTT test on human cell cultures A549 (lung carcinoma) and HCT116 (colorectal carcinoma). Camptothecin and daunorubicin were used as reference drugs. The value of the concentration inducing 50% inhibition of the cell growth (IC50, μM) was determined from the dose-response curves using GraphPad Prism 9 software. Compounds III 3 (R1=R2=Br, Ar=2,5-di-OMe-С6Н3,) III 4 (R1=R2=Br, Ar=4-F-С6Н4), III 6 (R1=Ме, R2=Н, Ar=2,4,5-tris-OMe-С6Н2), III 13 (R1=R2=Br, Ar=Ph), III 14 (R1=R2=Br, Ar=2,3-di-OMe-С6Н3) and III 16 (R1=R2=Br, Ar=Py) showed the best results for A549 and HCT116 cultures. The effect of the most active compounds III 3 and III 4 on the cell cycle and apoptosis was studied on Jurkat cell culture (human acute T-cell leukemia). Compounds III 3 and III 4 showed significant cytotoxicity against the Jurkat line in the resazurin test – 1.47 ± 0.06 and 4.56 ± 0.19 μM, respectively, comparable to the cytotoxicity of the reference drug camptothecin of 1.24 ± 0.05 μM. Based on the flow cytometry results, it is suggested that the effect is manifested by some (possibly reversible) cell cycle arrest in the presynthetic phase.

Organocatalytic Enantioselective Pictet–Spengler Reaction of α‐Ketoesters: Development and Application to the Total Synthesis of (+)‐Alstratine A

AbstractWe report herein an asymmetric Pictet–Spengler reaction of α‐ketoesters. In the presence of a catalytic amount of simple alanine‐derived squaramide and p‐nitrobenzoic acid, reaction of tryptamines with methyl 2‐oxoalkanoates afforded the corresponding 1‐alkyl‐1‐methoxycarbonyl tetrahydro‐β‐carbolines (THBCs) in high yields and ee values. A primary kinetic isotope effect (KIE=4.5) using C2‐deteurium‐labelled tryptamine indicates that rearomatization through deprotonation of the pentahydro‐β‐carbolinium ion could be the rate‐ and enantioselectivity‐determining step. A concise enantioselective total synthesis of (+)‐alstratine A, a hexacyclic cagelike monoterpene indole alkaloid, featuring this reaction as a key step, was subsequently accomplished. Remeasurement of the [a]D value of the natural product indicates that natural alstratine A is dextrorotatory rather than levorotatory as it was initially reported in the isolation paper.

Organocatalytic Enantioselective Pictet-Spengler Reaction of α-Ketoesters: Development and Application to the Total Synthesis of (+)-Alstratine A.

We report herein an asymmetric Pictet-Spengler reaction of α-ketoesters. In the presence of a catalytic amount of simple alanine-derived squaramide and p-nitrobenzoic acid, reaction of tryptamines with methyl 2-oxoalkanoates afforded the corresponding 1-alkyl-1-methoxycarbonyl tetrahydro-β-carbolines (THBCs) in high yields and ee values. A primary kinetic isotope effect (KIE=4.5) using C2-deteurium-labelled tryptamine indicates that rearomatization through deprotonation of the pentahydro-β-carbolinium ion could be the rate- and enantioselectivity-determining step. A concise enantioselective total synthesis of (+)-alstratine A, a hexacyclic cagelike monoterpene indole alkaloid, featuring this reaction as a key step, was subsequently accomplished. Remeasurement of the [a]D value of the natural product indicates that natural alstratine A is dextrorotatory rather than levorotatory as it was initially reported in the isolation paper.

Practical Stereoselective Synthesis of C3‐Spirooxindole‐ and C2‐Spiropseudoindoxyl‐Pyrrolidines via Organocatalyzed Pictet‐Spengler Reaction/Oxidative Rearrangement Sequence

AbstractA stereoselective synthetic route to chiral C3‐spirooxindole‐ and C2‐spiropseudoindoxyl‐pyrrolidines was accomplished by an enantioselective organocatalyzed Pictet‐Spengler reaction of tryptamines and isotryptamines followed by a diastereoselective oxidative rearrangement using eco‐friendly oxidants (i. e., NaOCl ⋅ 5H2O and Oxone®). This sequential reaction enables rapid access to chiral C3‐spirooxindole‐ and C2‐spiropseudoindoxyl‐pyrrolidines in a one‐pot process. A Wnt signaling inhibitory assay of the prepared enantioenriched spiro compounds demonstrated that they exhibited moderate activities.magnified image

Natural surfactants assisted an efficient synthesis of tetrahydro-β-carbolines

An expeditious protocol for the synthesis of structurally diversified β-carboline derivatives has been reported using a readily available natural surfactant medium. The synthesis of β-carboline derivatives in good yields under optimized conditions was carried out by the reaction of tryptamine with aldehydes in an aqueous extract of Acacia Concinna pods. The use of an aqueous medium, ease of purification, good yield and cost-effective reaction suggest for bulk scale production β-carboline derivatives.

Synthesis and Antibacterial Activity of 5-Aryl-4-[hydroxy(4-chlorophenyl)methylene]-1-[2-(1H-indol-3-yl)ethyl]pyrrolidine-2,3-diones

The reaction of tryptamine with aromatic aldehydes and 4-chlorobenzoylpyruvic acid methyl ester led to the formation of 5-aryl-4-[hydroxy-(4-chlorophenyl)methylene]-1-[2-(1H-indol-3-yl)ethyl]pyrrolidine-2,3-diones. The resulting compounds were tested for antimicrobial activity.

Antibacterial and antifungal activities of some novel imines of tryptamine

Abstract Novel Schiff bases such as N-cyclohexylidene-2(1H-indol-3-yl) ethanamine [TCH], 2-(1H-indol-3-yl)-N-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)ethanamine [TC], 2-(1H-indol-3-yl)-N-(1-phenylethylidene)ethanamine [TAP] were prepared by the condensation reaction of tryptamine with cyclo hexanone , camphor and aceto phenone. The imines were characterised by UV-Visible, FT-IR and H1NMR spectral data. All the three Schiff bases were screened for antibacterial (staphylococcus aureus, Bacillus substilis, salmoneila typhi and Proteus Vulgaris) and antifungal (candida alibicans, Aspergilus niger) activities by disc diffusion method. The results indicate that all imines exhibit significant antimicrobial activity.

Syntheses, in vitro urease inhibitory activities of urea and thiourea derivatives of tryptamine, their molecular docking and cytotoxic studies

Urease is an enzyme of amidohydrolase family and is responsible for the different pathological conditions in the human body including peptic ulcers, catheter encrustation, kidney stone formation, hepatic coma, encephalopathy, and many others. Therefore, the search for potent urease inhibitors has attracted major scientific attention in recent years. Urea and thiourea derivatives of tryptamine (1–25) were synthesized via reaction of tryptamine with different substituted phenyl isocyanates/isothiocyanates. The synthetic compounds were evaluated for their urease enzyme inhibitory activity and they exhibited good inhibitory potential against urease enzyme in the range of (IC50 = 11.4 ± 0.4–24.2 ± 1.5 μM) as compared to the standard thiourea (IC50 = 21.2 ± 1.3 μM). Out of twenty-five compounds, fourteen were found to be more active than the standard. Limited structure-activity relationship suggested that the compounds with CH3, and OCH3 substituents at aryl part were the most potent derivatives. Compound 14 (IC50 = 11.4 ± 0.4 μM) with a methyl substituent at ortho position was found to be the most active member of the series. Whereas, among halogen substituted derivatives, para substituted chloro compound 16 (IC50 = 13.7 ± 0.9 μM) showed good urease inhibitory activity. These synthetic derivatives were found to be non-cytotoxic in cellular assay. Kinetic studies revealed that the compounds 11, 12, 14, 17, 21, 22, and 24 showed a non-competitive type of inhibition. In silico study identified the possible bindings interactions of potential inhibitors with the active site of enzyme. These newly identified inhibitors of urease enzyme can serve as leads for further research and development.

Ab Initio QM/MM Modeling of the Rate-Limiting Proton Transfer Step in the Deamination of Tryptamine by Aromatic Amine Dehydrogenase.

Aromatic amine dehydrogenase (AADH) and related enzymes are at the heart of debates on the roles of quantum tunneling and protein dynamics in catalysis. The reaction of tryptamine in AADH involves significant quantum tunneling in the rate-limiting proton transfer step, shown by large H/D primary kinetic isotope effects (KIEs), with unusual temperature dependence. We apply correlated ab initio combined quantum mechanics/molecular mechanics (QM/MM) methods, at levels up to local coupled cluster theory (LCCSD(T)/(aug)-cc-pVTZ), to calculate accurate potential energy surfaces for this reaction, which are necessary for quantitative analysis of tunneling contributions and reaction dynamics. Different levels of QM/MM treatment are tested. Multiple pathways are calculated with fully flexible transition state optimization by the climbing-image nudged elastic band method at the density functional QM/MM level. The average LCCSD(T) potential energy barriers to proton transfer are 16.7 and 14.0 kcal/mol for proton transfer to the two carboxylate atoms of the catalytic base, Asp128β. The results show that two similar, but distinct pathways are energetically accessible. These two pathways have different barriers, exothermicity and curvature, and should be considered in analyses of the temperature dependence of reaction and KIEs in AADH and other enzymes. These results provide a benchmark for this prototypical enzyme reaction and will be useful for developing empirical models, and analyzing experimental data, to distinguish between different conceptual models of enzyme catalysis.

ChemInform Abstract: Synthetic Study on the T3P®‐Promoted One‐Pot Preparation of 1‐Substituted‐3,4‐dihydro‐β‐carbolines by the Reaction of Tryptamine with Carboxylic Acids.

AbstractA one‐pot procedure for the synthesis of 1‐substituted‐3,4‐dihydro‐β‐carbolines from tryptamine and the corresponding aliphatic and (hetero)aromatic carboxylic acids using T3P as the condensation reagent is reported.

Synthetic study on the T3P®-promoted one-pot preparation of 1-substituted-3,4-dihydro-β-carbolines by the reaction of tryptamine with carboxylic acids

A novel and efficient one-pot method has been developed for the synthesis of 1-substituted-3,4-dihydro-β-carbolines from tryptamine and a wide variety of carboxylic acids. The reaction was successfully applied to the synthesis of an important alkaloid harmalan as well as dihydro-eudistomin-U. This represents the first case in which 1-propanephosphonic acid cyclic anhydride (T3P®) has been used in the Bischler–Napieralski reaction. Unexpectedly it was observed that less than two equivalents of the T3P® reagent were sufficient for the two consecutive reactions.

ChemInform Abstract: Enantioselective Gold Catalyzed Cascade Construction of Pyrroloindoline Derivatives.

AbstractThe reaction of tryptamines with allenoamides in the presence of BINOL‐derived phosphoramidate ligated gold catalysts provides pyrroloindolines with enantioselectivities up to 99%.

Ultrasound Assisted Pictet–Spengler Synthesis of Tetrahydro‐β‐Carboline Derivatives

The synthesis of twelve tetrahydro‐β‐carboline derivatives 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l prepared via the Pictet–Spengler reaction is described. The reaction of tryptamine and a variety of arylaldehydes were carried out under ultrasonic irradiation and trifluoracetic acid catalysis at room temperature. These tetrahydro‐β‐carbolines have been synthesized in higher yields and shorter reaction times compared to the conventional method. Moreover, the reaction proceeded successfully even employing arylaldehydes with electron‐donating or electron‐attracting substituents which did not react under conventional method.

Mechanistic insights into a BINOL-derived phosphoric acid-catalyzed asymmetric Pictet-Spengler reaction.

The reaction of tryptamine and (2-oxocyclohexyl)acetic acid can be catalyzed by 3,3'-bis(triphenylsilyl)-1,1'-bi-2-naphthol phosphoric acid to give an asymmetric β-carboline. This reaction was first studied by Holloway et al. ( Org. Lett. 2010 , 12 , 4720 - 4723 ), but their mechanistic work did not explain the high stereoselectivity achieved. This study uses density functional theory and hybrid quantum mechanics/molecular mechanics calculations to investigate this reaction and provide a model to explain its outcome. The step leading to diastereo- and enantioselectivity is an asymmetric Pictet-Spengler reaction involving an N-acyliminium ion bound to the catalyst in a bidentate fashion. This interaction occurs via hydrogen bonds between the two terminal oxygen atoms of the catalyst phosphate group and the hydrogen atoms at N and C2 of the substrate indole group. These bonds hold the transition structure rigidly and thus allow the catalyst triphenylsilyl groups to influence the enantioselectivity.

ChemInform Abstract: Diastereoselective Syntheses of Indoloquinolizidines by a Pictet—Spengler/Lactamization Cascade.

AbstractThe reaction of tryptamines with aldehydes, generated in situ in the asymmetric conjugate addition of α,β‐unsaturated substrates with malonates, affords the tetracyclic products as single diastereomers.

A new insight on the hypochlorous acid scavenging mechanism of tryptamine and tryptophan derivatives

The reaction mechanisms of hypochlorous acid (HOCl) with several tryptophan and tryptamine derivatives, previously reported to scavenge this powerful oxidant, was investigated to determine whether ionic or radical pathways were involved. For this purpose, the reaction of tryptamine and tryptophan derivatives with HOCl was optimized and some compounds were isolated by HPLC and their structures assigned. In order to prevent possible radical reaction pathway, experiments have been carried in the presence of the radical trap TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl). The obtained results show that the reaction mechanisms are influenced by the type of structure and that a complex pathway is involved, in which both ionic and radical mechanisms can occur.